Editorial: Human Embryonic Stem Cell Cardiomyocyte Derivatives for Heart Regeneration — The Vital Source for Myocardial Tissue Engineering and Myocardium Repair

San Diego Regenerative Medicine Institute and Xcelthera announce Dr. Parsons’ Editorial, titled “Mending the broken heart – Towards clinical application of human embryonic stem cell therapy derivatives” (doi: 10.4172/2155-9880.1000e116), published in current issue of The International Open Access Journal of Clinical & Experimental Cardiology.

Human embryonic stem cell (hESC) research holds tremendous potential for tissue and organ regeneration and function restoration. Clinical applications of hESC therapy derivatives provide the right alternate for many incurable diseases & major health problems that the regular mode of treatment cannot. Each single one of those world-wide major health problems cost the health care system or taxpayers more than $10 billion annually. In particular, hESC cardiac derivatives are the only cell source so far that can regenerate the contractile heart muscle (known as cardiomyocytes), vital for cardiovascular repair.

Due to the prevalence of heart disease worldwide and acute shortage of donor organs or adequate human myocardial grafts, there is intense interest in developing hESC-based therapy for heart disease and failure. Recent advances and breakthroughs in hESC research have overcome some major obstacles in bringing hESC therapy derivatives towards clinical applications, including establishing defined culture systems for de novo derivation of clinically-suitable stable hESC lines from human blastocysts that have never been contaminated by animal cells and proteins, and direct conversion of such pluripotent hESCs into a large supply of clinical-grade functional human cardiac precursors and cardiomyocytes to be translated to patients for mending the damaged heart. The availability of human cardiomyocyte derivatives in high purity and large quantity with adequate potential for myocardium regeneration will facilitate myocardial tissue-engineering and accelerate the development of safe and effective cell-based therapy for heart disease and failure that affect millions of survivors and so far have no cure. It makes heart disease and failure possible to be the first major health problem to be resolved by clinical translation of the advances of hESC research. Such milestone advances and medical innovations in hESC research provide the only hope to many patients whose life-span is measured in months or years. Further improving policy making, transparency & fair competition of grant review process & government funding agencies, and funding situation for hESC research would drive the advances of medicine to provide new medical treatments for many devastating and life-threatening diseases. 

CIRM Flawed Grant Review --- Financial Conflicts Hostile Override Prop 71 & Stall Stem Cell Research

Although California State Stem Cell Agency -- California Institute for Regenerative Medicine (CIRM) was created by California Proposition 71 (Prop 71), CIRM has never done anything to implement CA stem cell research bond initiative, to prioritize Prop 71 stem cell research, as any government funding agency would or should have done by law. Absence of Prop 71 has been prominently featured in CIRM, from its website, public meetings & events, RFAs, unlawful or special interest eligibility criteria, grant review, grants working groups, scientific grants review officers, scientific reviewers, ICOC meetings, to $ billions of conflicts of interest (COI) awards, to any outcomes or results or publications of CIRM awards. $1.7 billion and 8 years later, California’s Prop 71 stem cell research or human embryonic stem cell (hESC) research remain stalled, stem cell research infrastructure un-built, hESC research lab unfunded, hESC therapy assets of Prop 71 priority unprotected, and promised stem cell therapy development unsupported by designated public/state government funds from Prop 71. For hard-working CA stem cell scientists who have strived to make stem cell research breakthroughs and advances in order to bring CA stem cell initiative as the only hope to many devastating and incurable diseases, as the only hope to those patients whose life-span is measured in months or years, we have never been able to access any support or funding designated by voter-approved Prop 71 to our research and our labs. What we have experienced with CIRM is not the support to our hESC research & advances approved by CA voters, but only a long struggle with the financial conflicts of interest of a flawed grant review process that has no transparency, no implementation for Prop 71, even hostile to hESC research of Prop 71; a long struggle with CIRM flawed grant review process biased towards CIRM board financial conflicts of interest that can only be found in the most corrupted government agency.

Human embryonic stem cells hold tremendous potential for tissue and organ regeneration and function restoration, therefore, provide treatment options and cures for many major health problems and life-threatening diseases that currently have no cure, such as heart disease and failure, diabetes, Parkinson’s disease, Alzheimer disease, ALS, and spinal cord injury. California voters passed a $3 billion stem cell bond initiative, known as Prop 71, for it, which shows that the majority of the public understand the therapeutic value of hESCs. Ironically, it is CIRM and its grants review groups and reviewers that do not understand Prop 71. Not only Prop 71’s hESC research grants applications approved by CA voters are unwelcome by CIRM grant review groups, CIRM external scientific reviewers and CIRM science officers’ merciless negative responses and destructions to hESC grant applications have also proven that CIRM grant review board is negligent, even hostile to Prop 71 (see attachments CIRMPreApp Review & CIRMApp below). To stall Prop 71 stem cell research approved by CA voters, CIRM board has not only issued COI RFAs [e.g., CIRM RFA12-02, 12-3, 12-04, 12-05, 12-09] and set unlawful special interest eligibility criteria [e.g., leadership awards need to be out of state, faculty awards need to have MD] to exclude or block Prop 71 stem cell research from applying for CA voter-approved funding, but has been using unlawful non-transparent Pre-application procedure to deliberately delay hESC research against the law [see CIRMParApp Review below].

CIRM > $1 billion awards to their financial ties without Prop 71 scientific merits are undeniable evidences for anti-transparent, anti-competition, anti-Prop 71, and anti-stem cell research of CIRM flawed non-transparent grant review. Prop 71 states that “Only the 15 scientist members of the Scientific and Medical Research Funding Working Group shall score grant and loan award applications for scientific merit”, however, CIRM board has been using only 5 reviewers not in the Scientific and Medical Research Funding Working Group to bias the selection of grant applications exclusively to CIRM board financial conflicts of interest against the law. Below please see samples of our hESC grant applications for lawful Prop 71 funding that have been deferred by CIRM non-transparent pre-application reviews since 2009 [see CIRMPreApp Review below]. Any single one of our hESC research grant applications meets the scientific merit of Prop 71 and is more crucial & urgent to Prop 71, to advance of stem cell research, and to patients than any grantees in any cycle of those CIRM RFAs. One excuse that CIRM used to cover up its non-transparent Pre-application to defer Prop 71 is that CIRM received too many applications [see CIRMPreApp Review below]. It is hard to imagine that CIRM with $20 M annual state budget, including ~$1 M luxury salaries for a chair and a president who both have been paid more than CA governor by taxpayer’s money, would cry about that they could not handle a few hundreds of applications, among which only a few dozen might have something to do with Prop 71. Among biased comments CIRM used to defer Prop 71, there are PI no drug development experience, reviewer-created COI or anti-Prop 71 or false issues, factual errors, even biased scores on word space information limited Pre-applications using few COI reviewers outside the CIRM grant working group against the law. CIRM has awarded > $1 billion to those without Prop 71 scientific merits using a flawed grant review process to deliberately defer urgent hESC research, so CIRM board members special financial interests to CA Prop 71 for cash help, such as Capricor, UC Davis, Stem, Bluebird, can override Prop 71 and stall stem cell research. Capricor did not have a single piece of scientific evidence that their tissue-derived cells can become beating heart muscle as hESCs do. UC Davis did not address the major issue of immunogenicity for their MSCs and did not have a single piece of scientific evidence that their MSCs can regenerate as hESCs do. STEM did not have a single piece of scientific evidence that their adult cells can repair lost nerve tissue and function as hESCs do. Robbin/Joseph Wu of Stanford U did not generate any approach of deriving cardiomyocytes from hESCs that offers any benefits in efficiency, stability, safety or manufacturing to the other systems as we did. None of those biased comments in CIRM Pre-application reviews that CIRM used to defer CA urgent Prop 71 stem cell research have applied to their COI awards (~ $20 M each) that would be urgent to none but CIRM board members’ special financial gains. 

Why would CIRM CFO Matt Plunkett, former CFO of iPierian, waste $ Ms of CA state funds to withhold Prop 71 funds from commercial validation of hESC assets and therapy using special interest eligibility requirement outside of Prop 71 (see below CIRM application SP1-06442)? iPierian, an iPS cell reprogramming company founded by ISSCR (International Society for Stem Cell Research) board members that include Larry Goldstein’s frequent Harvard guests who severed on CIRM review board, such as George Daley, Amy Wager, Kevin Eggan, Chad Cowan, as well as Deepak Srivastava and Shinya Yamanaka of UCSF & Gladstone, who have not only cooked iPS stem cell fraud research papers using their academy member and editor positions, but have also cooked $Ms NIH & CIRM awards to iPS cells of Gladstone/UCSF & UCSD & Scripps & Cellular Dynamics International, with ISSCR current President Rudy Jaenisch of Harvard and his another protégée Lauren Boyer (on $Ms of Deepak Srivastava NIH iPSC award). If we think David Petraeus’s juicy Pentagon right after the election is shocking exposure, let’s see Irving Weissman’s juicy Pentagon in CIRM. Amy Wager (Harvard, the CIRM reviewer, another woman tied to Irving Weissman of Stanford), Catriona Jamieson (UCSD, ~$30M CIRM awards), Nobuko Uchida (Stem Cell Inc, ~$20M CIRM award), Alexandra Capela (Stem Cell Inc., ~$20M CIRM award), and Tannishtha Reya (UCSD, ~$6M CIRM follow the husband lead award) have juiced Bob Klein & CIRM for hundreds of millions from Prop 71 to Irving Weissman and Larry Goldstein and their consortiums such as Sanford Consortium. No wonder that CIRM lucrative RFAs make Prop71 stem cell research impossible to get lawful public funds whereas give unlawful stem cell frauds the green light (see our previous posts).

We meet Prop 71 eligibility and essential Prop 71 stem cell asset commercial validation criteria that none of CIRM’s funded teams have. Why would CIRM CFO Matt Plunkett want to discuss our eligibility criteria? If we take a look at CIRM board members’ financial disclosure public information, it reveals their far and wide special interest connections, from big Pharms & google venture to a broad range of investment firms. It also reveals CIRM board members’ investment firms’ connections with CIRM grantees’ companies. It is shocking to realize from these public information that, while the public, CA voters, & stem cell scientists are counting on CIRM board members to ensure Prop 71 go to stem cell research, those CIRM board members are actually take-over artists on management team scam & investment fraud to make profit on Prop 71 public fund. If we wonder how a Massachusetts gene-therapy company Bluebird Bio tapped California's stem cell agency for cash help, maybe we should take a look at their investment and management ties, such as Shire Reg Med in Dublin, Ireland and In vivo, to CIRM board members Duane Roth, Matt Plunkett, and chair Jon Thomas. No wonder CIRM keeps deferring Prop 71 stem cell research grant applications using non-transparent pre-applications, so Matt Plunkett & CIRM board members’ own management scam in Bluebird or iPierian can get cash help from Prop 71. CRM board members’ $10Ms or more to take over management control prior to awards, such as Geron, Stem Cell Inc, Viacyte, and Bluebird, have provided the evidences that CIRM $10M special interest eligibility requirement outside of Prop 71 [e.g., CIRM RFA 12-05 & 12-09] is only to sink stem cell biotech and block competition against government anti-trust laws. It is shocking to realize what CIRM CFO Matt Plunkett’s intention to discuss eligibility criteria with Regenerative Medicine Startups of Prop 71 is actually trying to tell our emerging growth startups that we are not eligible according to his COI criteria because we have not been taken over by his greedy management scam yet!

We have been hearing a lot of stem cell scams from companies invited by Stem Cell Meeting on the Mesa (SCMOM) organized by CIRM, alliance for regenerative medicine (ARM), and Duane Roth of UC connect and Sanford Consortium for Regenerative Medicine, which, by contrast, deliberately excluded or blocked Regenerative Medicine Startups of Prop 71 stem cell research (see our previous posts). What makes those snake oil purveyors or stem cell con men, such as Pluristem stem cells in placenta, Medistem & Neostem stem cells in umbilical cord, Cytori stem cells in fat, Histogen stem cells in skin, and Cellular Dynamics iPS fraud, so blatantly seek publicity against scientific evidences? These so-called stem cell biotech companies all share a management scam website that features a well-assembled management team but no stem cells or stem cell research, very similar to the website of Sanford Consortium for Regenerative Medicine of Duane Roth & UC connect. If we take a look at Duane Roth’s investment firm Roth Capital Partners, we would see that these blatant stem cell scam companies sourced from UC connect & SCMOM are actually backed by Roth Capital’s $Ms of big money and management team scam, such as ~$50 M to Pluristem, ~$8 M to Neostem. Duane Roth, the CEO of UC connect and vice chair of CIRM, is also on the board of Sanford-Burnham, former La Jolla cancer institute. If we wonder why Geron would have change of heart to abandon their stem cell programs and solely bet on cancers only < 3 months after Geron received $25M CIRM award. Maybe it is helpful to know that Roth Capital invested $100M to Geron in Dec, 2010, around the same time CIRM RFA 10-03: CIRM TARGETED CLINICAL DEVELOPMENT AWARDS would only accept Geron’s grant and deferred all other applications, even though our hESC therapy product application had better scientific merit to work for patients (see below). In 2011, CIRM & Duane Roth gave Geron $25 M award, even though they knew that Geron’s oligodendrocytes turned into non-functional fibroblasts and had already failed their clinical trial for spinal cord injury, even though they knew that it was waste of $25M of taxpayers’ money and public fund. Similarly, in Dec., 2011, Roth Capital invested $10M to Stem Cell Inc., about the same time CIRM would only accept CIRM board members’ Disease Team Therapy Development Awards Phase II grant applications, while blocked our hESC lawful stem cell therapy development application that had the scientific merit of Prop 71 (see below). It turned out later on that none of those CIRM prioritized Phase II applications had any scientific merit of Prop 71 but COI ties (see CIRM award announcements in 2012). In 2012, CIRM, Duane Roth, and Bob Klein gave Stem Cell Inc. $40 M awards despite that Stem Cell Inc. had no scientific data to back their clinical trial claims and their grants had no scientific merits of Prop 71, despite that they knew that it was waste of $40M of taxpayers’ money and public fund. Roth Capital’s investment and Geron/Stem management team changes, including their CEOs, tell us that CIRM board member Roth had taken over both Geron and Stem’s management and company controls before CIRM & Roth cooked CIRM awards to their own management companies. Roth’s close tie with Sanford-Burnham, a La Jolla cancer research institute, and management control over Geron would explain that Geron abandoned their stem cell programs and solely bet on cancers in Nov., 2011, because their sole motivation to cook $25M of CIRM award to Geron was for their executives’ financial interest to profit on stock/investment/management scam, not even any slightest concerns for stem cell research and waste of taxpayers’ money of Prop 71. Soon after Sept. 2012 when Geron failed their cancer drug, Biotime, a close alliance with Duane Roth/Sanford-Burnham, quickly formed Biotime acquisition to take over Geron’s stem cell assets backed by $Ms of private investment. Their ongoing drama is very likely only the prelude to CIRM next cooked award and their board members’ management takeover scam, at the cost of Prop 71 stem cell research approved by CA voters and taxpayers’ money. Those CIRM board members like Duane Roth & Matt Plunkett have corrupted California stem cell agency and have made big profits on Prop 71/public fund by cooking CIRM awards to their own investment/management scams & stock frauds, while they used CIRM flawed non-transparent grant review featuring biased pre-application [see CIRMPreApp Review below] and their special interest eligibility criteria [e.g., CIRM RFA 12-02, 03, 04, 05, 09] against law to make the gullible public and stem research scientists believe that their greedy hostile takeovers to stall Prop 71 stem cell research are any lawful competition but corruption. Please see attachments at SDRMI wordpress.

Cooking Awards --- Sanford Consortium’s Fictitious Stem Cell Research & Directors’ Financial Ties Far and Wide

California Institute for Regenerative Medicine (CIRM) $10M award to Viacyte in most recent round is a laudable positive move towards the right path of California stem cell bond initiative, known as Proposition 71 (Prop 71), on the road to commercialize stem cell therapy for diabetes currently affecting ~ 250 million people worldwide. It is probably the only bright spot among hundreds of millions of CIRM conflicts of interest (COI) awards repressive to Prop 71 that have quickly doubled California state’s debt to > $1.6 billion since CIRM’s new Chair Jon Thomas took office over a year ago. However, it did not come without cooking the financial ties with CIRM Directors. Its advocacy for CA stem cell initiative as cures to type I diabetes patients is also tarnished by CIRM board’s equal amount of COI award to a out of state gene-therapy company Bluebird Bio that has no relationship whatsoever to CA stem cell initiative or Prop 71, but has close ties to CIRM board (e.g., Bertran Lubin) from Oakland CHO/UCs and Sanford Consortium directors (e.g., Larry Goldstein & Duane Roth). Such real financial ties to CIRM directors have also dampened any enthusiasm about CIRM very publicized move to turning CA stem cell initiative into any cures, and raised the eyebrow if CIRM’s initiative to steer towards industry by partnership is only to help CIRM directors to extend their financial ties far and wide, and if it is only to make it easier for CIRM directors to recreate a industry replica for what they have done in academia, which so far has yielded virtually zero results with CA state $1.6 billion of investment.

For simple-minded gullible public, neither Prop 71 nor scientific merit can help understand CIRM $1.6 billion of awards. It is a conflict of interest (COI) phenomenon that can only be explained by their financial ties to CIRM board. The award cooking processes actually started far before CIRM RFAs were even issued. If we wonder how a Massachusetts gene-therapy company tapped California's stem cell agency for cash help, maybe we should take a look at Larry Goldstein & Duane Roth’s stem cell meeting on the mesa (SCMOM) organized by CIRM, Sanford Consortium for Regenerative Medicine (SCFRM), and Alliance for Regenerative Medicine (ARM). Those CIRM future grantees had already been printed on SCMOM invited list a year ago. SCMOM is a meeting full of Sanford directors and their organizers’ academia and industry ties with financial interests to CA Prop 71, therefore, has no room to accommodate any CA’s Prop 71 stem cell research since its inception in 2005. After last year’s SCMOM, CIRM issued 6 consecutive COI RFAs, 3 of which being instructed to boldly exclude Prop 71 stem cell research against the law, to accommodate Sanford directors and their organizers’ academia and industry interests to CA Prop 71 for cash, which shows that Larry Goldstein and Duane Roth’s SCMOM featuring CIRM president Alan Trounson, vice president Ellen Feigal, and chair Jon Thomas as well as Larry Goldstein’s close professional associates (e.g., Craig Venter, Robert Wechsler-Reya, Catriona Jamieson, Vanessa Hayes, Adam Engler, Kristin Baldwin) is not just a simple stem cell meeting as simple-minded gullible public & stem cell scientists would think. The dynamics of their strategic partnership movement afterwards have not been just coincidence. There were Shire or investor partner or capital raising rounds, organized by Duane Roth/UC connect or Janssen or ARM, to companies financially tied to directors of CIRM and/or Sanford. David Davidson from Genzyme moved to Bluebird and forged connections with Oakland & UCLA directors. Duane Roth moved to Sanford Burnham board; Sanford Burnham’s Paul Laikind moved to Viacyte; Evan Snyder of Sanford Burnham moved to the board of Alan Trounson’ company ISCCO; John Reed, Mark Mercola, Clive Svedensen, and Larry Goldstein were met at Sanford Burnham, so they could be all together ready to ripe their cooked awards from CIRM.

Why would, in 2012, CIRM and Alan Trounson still continue to implement a 3 year-old 2009 leadership award for out-of-state fictitious stem cell scientists, while completely ignore any CA stem cell research leaders and their endeavors for Prop 71 stem cell research? We may remember Irving Weissman said something like that he wanted to get all the stem cell experts coming to CA. REALLY? If we know who are among those Irving Weissman had CIRM bribed into CA with public money, maybe Irving Weissman meant to say that he wanted to get all his professional associates coming to CA to help him cooking CIRM awards. Larry Goldstein, as a permanent member on Irving Weisman’s ISSCR (International Society for Stem Cell Research) board, did not just invite Robert Wechsler-Reya once, he invited him so many times that even I could not completely miss his talks. In 2009, in order to understand why he was the only speaker from out of state invited by Larry Goldstein and Alan Trounson, my gullible brain tried hard to find any stem cell research or stem cell in his talk at SCMOM, but did not succeed. It was not until ~ 6 months later when Alan Trounson gave Robert Wechsler-Reya $6 million CIRM leadership award without going through the regular grant review process, we were able to realize that they were cooking CIRM leadership award at SCMOM. But I still could not understand why Larry Goldstein, who is notoriously repressive to stem cell research at UCSD and SCFRM, would be so fond of Robert Wechsler-Reya and his wife, not only guaranteed a out-of–state person without any stem cell research experience $ 6M from CA state stem cell initiative to become Tumor Program Director at Sanford Burnham, but also had his wife promoted to professor at UCSD Pharmacology Department. It was not until Robert Wechsler-Reya wife’s professional tie to Irving Weissman became unveiled, just like Catriona Jamieson, Fred Gage, and some others around Larry Goldstein and Duane Roth, I could realize why Larry Goldstein and Duane Roth guaranteed their residency at SCFRM, while despotically claim SCFRM, built with public state money for stem cell research, cannot accommodate any San Diego’s stem cell research against law. Without their professional and financial ties to ISSCR, CIRM & review boards, ARM & big Pharms, even NIH, without their constantly inviting/bribing their COI ties & forging/polishing COI strategic partnership in the name of stem cell meeting/research, it is hard to imagine that, with virtually no stem cell research results, Larry Goldstein & Irving Weissman’s inner circle could be able to snap up > $500M cooked awards from CIRM just for those who have direct connection to ISSCR board, including ~ $40M to Larry Goldstein and his associates, ~ $ 70 M to Irving Weissman and his company, ~ $30 M to Catriona Jamieson and more to other offspring or professional associates of Irving Weissman.     

If we, the people, and the government for the people, count on Duane Roth and other CIRM directors to do their job, to ensure Prop 71 cash go to stem cell research, not to their own COI ties, what they have done and what SCMOM have accommodated are telling us that we are mistaken. The one thing SCMOM invited speakers share in common is not stem cell research, but their far and wide professional and financial ties to Larry Goldstein and Sanford directors. SCMOM should be called CIRM grantee meeting, because it accommodates CIRM past and future cooked grantees. If the public and CA state government wonder where our $1.6 billion has gone to and why there is no result, it is the meeting they should attend. It is the meeting not showing progresses/advances of stem cell research, not showing cures/hope for patients, but waste of hundreds of millions of public/state money on useless research or Sanford consortium fictitious stem cell research, and continuing waste of hundreds of millions of public/state stem cell research money on waiting cooked awards for CIRM COI RFAs on iPS/adult cells. It is a meeting that the Nobel committee should also eavesdrop too, because then they could hear the truth about those so-called biggest breakthrough of adult stem cell research hailed by opponents of Prop 71 stem cell research, hear that the induced pluripotent stem cells (iPS cells) are actually useless for patients, having structural defects, oncogenes, genes for diseases & tumors, mutations for genes maintaining genomic stability, etc. SCMOM could accommodate flies (e.g., Leanne Jones of Salk Institute), mouse/adult cells (e.g., Alessandra Sacco of Sanford Burnham/Stanford), cancer (e.g., Robert Weschsler-Reya of Sanford Burnham, Catriona Jamieson of UCSD), and iPS/adult cells (e.g., Kristein Baldwin of Scripps, Ken Zhang of UCSD, Vanessa Hayes of Craig Venter, Birgitt Schuele of Parkinson’s institute). SCMOM could accommodate stem cell research imposters and stem cell conman’s big claims with virtually no data (e.g., Fyodor Urnov of Sangamo’s cardiomyocytes from pluripotent cells). SCMOM could not accommodate Prop 71 stem cell research but something close to a hoax that our taxpayers should not have to pay.

Strong Hold on Financial Conflicts --- UC Fictitious Stem Cell Programs and Yudof’s Excuses

Although he is the former chair, Bob Klein should have his rights to speak freely on CIRM (California Institute for Regenerative Medicine) ICOC board meetings, voice his opinions, and advocate for patients. However, Bob Klein is also on ISSCR (International Society for Stem Cell Research) board. That Bob Klein specifically picked Stem Cell Inc - a company of ISSCR former president and CIRM board member - and used his influence as former CIRM chair to successfully lobby $ 40 millions to one single company of his professional association is anything but advocacy for patients. Not only Bob Klein has done it on a public stage, but Bob Klein has also done it by falsifying CIRM grant review statements against scientific evidences. Bob Klein has done it to show the public that CIRM board can award their own financial conflicts of interests against the scientific merits of Prop 71, against the law. Bob Klein has done it to show the public that all the CIRM grant eligibility/review criteria/scores, that have been used by CIRM grant review to stall Prop 71 stem cell research under the public sight, do not apply to CIRM board members’ institutions and companies. Bob Klein has done it to show the public that CIRM board members’ institutions and companies are exempted from the law requirements and scientific merits of Prop 71. Contrary to Alan Trounson’ public comment that there is no evidence for conflicts of interest, Bob Klein has done it by staging a very dramatic public show to provide evidences for conflicts of interest, which is synergized by Alan Trounson’ extraordinarily exceptions that he has given and has given exclusively only to CIRM board members, including Capricor, UCI, and Stem Cell Inc, against the scientific merits of Prop 71 [e.g., none of these awards are for human pluirpotent stem/progenitor cells required by the law/Prop 71]. If these financial conflict evidences are not enough, Ellen Feigal and UC Davis chancellor Claire Pomeroy and Francisco Prieto have also embezzled $50 millions of Prop 71 to a cluster of UC Davis snake oil purveyor against any scientific merits of Prop 71 in one single round of CIRM awards.

University of California (UC)’s firm grip to about half of CIRM awards, total ~ $800 millions from Prop 71 and ¾ of these awards have nothing to do with Prop 71, would not be possible without 12 of their Directors on CIRM board to represent their strong financial conflicts of interest, including Duane Roth, CEO of UC connect; Shlomo Melmed, associate dean of UCLA and director at Cedars-Sinai Medical Center; Robert Birgeneau, chancellor of UC Berkeley; Carmen Puliafito, dean of the Keck School of Medicine; David Brenner, vice chancellor and dean of UCSD; Susan Bryant, vice chancellor of UCI; Sam Hawgood, dean and vice chancellor of UCSF; Claire Pomeroy, vice chancellor of UC Davis; Eugene Washington, vice chancellor and dean of UCLA; Sherry Lansing, a Regent and chair of UC; Francisco Prieto, clinical professor at UC Davis; Oswald Steward, chair and director of UCI. UC’s strong financial interest representation in CIRM board is in staring contrast to UC fictitious stem cell programs/centers where human embryonic stem cell (hESC) research of Prop 71 virtually does not exist. So, without a robust hESC research program, how did Larry Goldstein get ~ $30 million awarded to himself from CIRM without having to do anything? With ~ $800 millions of taxpayers’ money that is enough to jump start many robust competitive hESC research programs or Regenerative Medicine start-ups, why would UC shut down hESC research labs (see below UC president Yudof’s excuse)? With mass amount of empty research spaces to offer, why could not UC, the biggest beneficiary of Prop 71, accommodate hESC research (see below UC president Yudof’s excuse)?

CIRM has awarded $1.2 billion out of 1.6 billion to those without Prop 71 scientific merits using a flawed grant review process that has zero implementation for Prop 71, even hostile to Prop 71 stem cell research. Who are selecting those biased CIRM awards using their CIRM sponsored meetings & CIRM board conflict of interest connections? What the public may not know is the despotic power of those professors as stem cell program/center directors acting on their financial conflicts of interest. As we know, Larry Goldstein had lots of talks about his fictitious astrocytes for > $10M CIRM ALS award with virtually no results [e.g., not even a single piece of data to show his cells express astrocyte markers in his ~ 1 hr on stage talk at world stem cell summit, he admitted himself publicly not working for ALS either]. And Larry Goldstein’s professional associate Anjana Rao, an immunologist and impostor for other stem cell scientists in San Diego UT, has cheated $Ms from CIRM with her fictitious stem cell research just because of her close connection with Larry Goldstein. With their tens of millions of financial benefits at stake, how likely do you think Larry Goldstein’s meeting committee for Stem Cell Meeting on the Mesa (SCMOM) would be able to perform any unbiased activities for scientific presentation? Both Anjana Rao and Larry Goldstein have $ Ms of CIRM awards for their fictitious stem cell research that has virtually no stem cell research results, no wander SCMOM cannot accommodate hESC research advances (see below poster submission for SCMOM). SCMOM’s hostile to hESC research is evident if check their invited list selected not based on the sciences but based on financial conflicts of interests with their senior organizers, committee members, directors, and close professional associates, so meeting organizers’ and CIRM board members’ close professional associates would be well accommodated for hundreds of millions of awards.

Sanford Consortium for Regenerative Medicine (SCFRM) is built with public stem cell research fund and supposed to open to all stem cell researchers in San Diego, open for collaboration, open for stem cell research advances. However, a year after the grand opening of "collaboratory", it remains as their senior directors’, such as Evan Snyder and Larry Goldstein, extended definition/territory for their own labs for the sole benefit of their institutes’ financial interest. Inconsistent to their deceptive idol-like faces in public, those directors’ un-collaborative behavior acting on their real financial conflicts of interest is nothing unfamiliar. Did I hear that Jean Loring claimed to sue Burnham officials if I would ever gain access to Burnham stem cell center supported by NIH funding that I was a major contributor to get that NIH center grant when I was at Burnham? Did I hear that Larry Goldstein claimed that I was not allowed to use UCSD stem cell center when I was at UCSD? Did I hear that Larry Goldstein used his despotic power as UCSD stem cell director to send mass emails to UCSD chancellor, deans, faculty to threat anybody who would give me a faculty position and lab spaces to allow me to administrate my NIH grants on human embryonic stem cell research, while he claimed himself publicly as a stem cell scientist, stem cell director, and supportor of hESC research?

Like SCMOM, Vincent Chen is just another episode of such severe conflicts of interest with those in power and abuses that power; either as director, mentor, or senior collaborator. Looking back on my mentor research scientist career development award (NIH K01 AG024496) in a field so controversial so money-driven, I would like to record here those examples of conflicts of interest that I wish it would be otherwise,

Conflicts of interest example 1: PI’s senior mentor Dr. Jean Loring had her close friends in or connected to NIH grant review committee [e.g., Mahendra Rao, former NIA & Director of CRM in NIH] to put the critique in summary statement to have the PI to identify her as the specific senior mentor for her K01 award. Dr. Jean Loring had financial or other interest in Dr. Parsons’ research/application, as evidenced by that she was able to use her advantages in senior position and resources to claim credits, including authorship & grants, for PI’s stem cell research, and was promoted to Professor & Center Co-Director at Sanford Burnham Medical Research Institute (former Burnham Institute) and received ~ 3 millions stem cell center grant from NIH without having to put the PI on the center grant. In fact, Dr. Loring used her advantage senior position as professor & stem cell center co-director to exclude the PI from using NIH-funded stem cell center resource for her stem cell research. Dr. Jean Loring has never fulfilled any mentor responsibility as written in her mentor support letter to NIH, and has used her advantages in senior/director position and resources to prevent the PI from fulfilling the career goal of K01 award to become an independent investigator or assistant professor/faculty due to conflicts of interest.

Conflicts of interest example 2: PI’s senior mentor Dr. Evan Snyder has financial or other interest in Dr. Parsons’ research/application, as evidenced by that he was able to use his advantages in senior position and resources to claim credits for all PI’s stem cell research, and was promoted to Center Director at Sanford Burnham Medical Research Institute (former Burnham Institute) and received ~ 3 millions stem cell center grant from NIH without having to put the PI on the center grant. In fact, Dr. Evan Snyder has used his advantages in senior mentor/director position to claim credits, including authorship and grants, for PI’s stem cell research, such as multi-millions of CIRM and NIH grants, collaboration/contracts with other senior collaborators, alliance and consortium, and donations or sponsorship/partnership from foundations and big Pharms, on which he has never included the PI or he has never obtained any collaboration agreement or consent from the PI. Dr. Evan Snyder has never fulfilled any mentor responsibility as written in his mentor support letter to NIH, but has spent >$30,000 of PI’s K01 award for his own lab use (although he was not supposed to according to K01 contract). Dr. Evan Snyder has used his advantages in senior/director position and resources to prevent the PI from fulfilling the career goal of K01 awards to become an independent investigator or assistant professor/faculty due to conflicts of interest.  

Conflicts of interest example 3: PI’s senior mentor Dr. Stuart Lipton has financial or other interest in Dr. Parsons’ research/application, as evidenced by that he was able to use his advantages in senior mentor/director position and resources to claim credits, including authorship and grants, for PI’s stem cell research, such as NIH center grants (e.g., Burnham NIH PD center) and multi-millions of CIRM grants, collaboration/contracts with other senior collaborators, alliance and consortium, and donations or sponsorship/partnership from foundations and big Pharms, on which he has never included the PI or he has never obtained any collaboration agreement or consent from the PI. In fact, Dr. Stuart Lipton has never fulfilled any mentor responsibility as written in his mentor support letter to NIH. Dr. Stuart Lipton has used his advantages in senior/director position and resources to prevent the PI from fulfilling the career goal of K01 awards to become an independent investigator or assistant professor/faculty due to conflicts of interest.  

Conflicts of interest example 4: PI’s senior mentor Dr. Yang Xu has financial or other interest in Dr. Parsons’ research/application, as evidenced by that he was able to use his advantages in senior position and resources to claim credits for PI’s stem cell research, and was promoted to Professor at University of California at San Diego. In fact, Dr. Yang Xu, who lacks appropriate stem cell research expertise, has used his advantages in senior mentor position and resources to claim credits for PI’s stem cell research for multi-millions of CIRM grants, on which he has never included the PI or he has never obtained any collaboration agreement or consent from the PI. Dr. Yang Xu has never fulfilled any mentor responsibility as written in his mentor support letter to NIH, but has used his advantages in senior position and resources to prevent PI from getting promotion/faculty position & research/lab spaces in UCSD to administrate her NIH grants, and has spent ~ $50,000 of PI’s K01 award for his own lab use (although he was not supposed to according to K01 contract). Dr. Xu has used his advantages in senior position and resources to prevent the PI from fulfilling the career goal of K01 awards to become an independent investigator or assistant professor/faculty due to conflicts of interest.  

Conflicts of interest example 5: PI’s senior mentor Dr. Prue Talbot, who lacks appropriate stem cell research expertise, has financial or other interest in Dr. Parsons’ research/application, as evidenced by that she was able to use her advantages in senior/director position and resources to claim credits for PI’s stem cell research to get multi-millions of CIRM grant funded as UCR stem cell director, on which she has never included the PI or she has never obtained collaboration agreement or consent from the PI. In fact, Dr. Prue Talbot has never fulfilled any mentor responsibility as written in her mentor support letter to NIH, but has involved in shutting down of PI’s hESC research lab at UCR and holding PI’s stem cells and research equipments in UCR without license agreement due to conflicts of interest. Dr. Talbot has used her advantages in senior/director position and resources to prevent the PI from fulfilling the career goal of K01 awards to become an independent investigator or assistant professor/faculty due to conflicts of interest. 

Frenzy over Reprogramming --- Nobel Prize Condescended to Cooked Stem Cell Fraud

The frenzy over induced pluripotent stem cells (iPS cells) in last few years was finally topped by Monday’s Nobel Prize announcement to most disbelief, which shows that the Nobel committee is only human and makes mistakes too. It is the sad consequence of irresponsible research from a combination of failure in knowledge, scientific conduct, originality, and peer review. It is the cooked result from lack of open discussion & dialogue, transparency, open public policy & view & opinion, open & unrestricted scientific ground, and open mind. It is ISSCR (International Society for Stem Cell Research) and few well-connected big names’ forced monologue cooked to appeal the political need and interest of opponents of human embryonic stem cell (hESC) research. It is erosion of scientific integrity and public trust. It is degraded of sciences and Nobel Prize. It does not take a genius or a Nobel committee to tell iPS cell is fraud. Yamanaka did not have any scientific data for the normality and stability of iPS cells that have been used to differentiate normal stem cells from abnormal cancer cells when it was rushed to publish in Cell, so it would come in handy for the political climate of Bush Administration and for those against hESC research to stall human embryonic stem cell research. Yamanaka even proved himself that DNA integrity is damaged and DNA damage check is compromised in iPS cells, so iPS cell is a hoax and he is irresponsible. So far, there is no scientific evidence that iPS cells are stem cells, nor iPS cells can cure any disease or be used for medicine, nor Yamanaka generated any cells work for any diseases for any imminent clinical trial. Far cry from 2010 when Nobel committee gave the IVF pioneer Robert Edwards his well–deserved Nobel Prize recognition, in 2012, Nobel committee has condescended to give Nobel Prize to the biggest stem cell conman. See our previous posts. Also See california stem cell report and Knoepfler stem cell blog for other opinions.

Turning Pluriptoent Human Embryonic Stem Cells into a Large Supply of Plastic CNS Derivatives for Cell Therapy

San Diego Regenerative Medicine Institute and Xcelthera announce the publication of Dr. Parsons’ original research article supported by the National Institutes of Health, titled “An Engraftable Human Embryonic Stem Cell Neuronal Lineage-Specific Derivative Retains Embryonic Chromatin Plasticity for Scale-Up CNS Regeneration”, in Journal of Regenerative Medicine & Tissue Engineering.

Human stem cell transplantation represents a promising therapeutic approach closest to provide a cure to restore the lost nerve tissue and function for a wide range of devastating and untreatable neurological disorders. However, to date, lack of a clinically-suitable source of engraftable human stem/progenitor cells with adequate neurogenic potential has been the major setback in developing effective cell-based therapy as a treatment option for restoring the damaged or lost central nervous system (CNS) structure and circuitry. The traditional sources of engraftable human stem cells with neural potential for transplantation therapies have been multipotent human neural stem cells (hNSCs) isolated directly from the human fetal CNS. However, cell therapy based on CNS tissue-derived hNSCs has encountered supply restriction and difficulty to use in the clinical setting due to their limited expansion ability and declining plasticity with aging, potentially restricting the tissue-derived hNSC as an adequate source for graft material.

Alternatively, the pluripotent human embryonic stem cells (hESCs) proffer cures for a wide range of neurological disorders by supplying the diversity of human neuronal cell types in the developing CNS for regeneration and repair. We must bear in mind that the pluripotent hESC itself cannot be used for therapeutic applications. It has been recognized that pluripotent hESCs must be transformed into fate-restricted derivatives before use for cell therapy. However, realizing the therapeutic potential of hESC derivatives has been hindered by the current state of the art for generating functional cells through multi-lineage differentiation of pluripotent cells, which is uncontrollable, inefficient, instable, highly variable, difficult to reproduce and scale-up, and often causes phenotypic heterogeneity and instability, hence, a high risk of tumorigenicity following transplantation. Under protocols presently employed in the field, the prototypical neuroepithelial-like nestin-positive hNSCs, either isolated from CNS in vivo or derived from pluripotent cells in vitro via conventional multi-lineage differentiation, appear to exert their therapeutic effects primarily by their non-neuronal progenies through producing trophic and/or neuroprotective molecules to rescue endogenous dying host neurons, but not related to regeneration from the graft or host remyelination.

We recently reported that pluripotent hESCs maintained under a defined platform can be uniformly converted into a cardiac or neural lineage by small molecule induction. This technology breakthrough enables well-controlled generation of a large supply of neuronal lineage-specific derivatives across the spectrum of developmental stages direct from the pluripotent state of hESCs with small molecule induction. Having achieved uniformly conversion of pluripotent hESCs to a neuronal lineage, in this study, the expression and intracellular distribution patterns of a set of chromatin modifiers in the hESC neuronal lineage-specific derivative hESC-I hNuPs were examined and compared to the two prototypical neuroepithelial-like hNSCs either derived from hESCs in vitro or isolated directly from the human fetal CNS in vivo. These hESC-I hNuPs expressed high levels of active chromatin modifiers, including acetylated histone H3 and H4, HDAC1, Brg-1, and hSNF2H, retaining an embryonic acetylated globally active chromatin state. Consistent with this observation, several repressive chromatin remodeling factors regulating histone H3K9 methylation, including SIRT1, SUV39H1, and Brm, were inactive in hESC-I hNuPs. These Nurr1-positive hESC-I hNuPs, which did not express the canonical hNSC markers, yielded neurons efficiently (> 90%) and exclusively, as they did not differentiate into glial cells, such as astrocytes, and oligodendrocytes. Following engraftment in the brain, hESC-I hNuPs yielded well-dispersed and well-integrated human neurons at a high prevalence. No graft overgrowth, formation of teratomas or neoplasms, or appearance of non-neuronal cell types was observed following engraftment. Transplanted wild type mice developed hyper-active behavior, such as fast movement and fast spin, which also suggested that transplanted human neuronal cells had survived and integrated into the mouse brain to function and control mouse behavior. By contrast, the prototypical neuroepithelial-like nestin-positive hNSCs derived either from hESCs or CNS can spontaneously differentiate into a mixed population of cells containing undifferentiated hNSCs, neurons (10-30%), astrocytes, and oligodendrocytes in vitro and in vivo. These observations suggest that, unlike the prototypical neuroepithelial-like nestin-positive hNSCs, these in vitro neuroectoderm-derived Nurr1-positive hESC-I hNuPs are a more neuronal lineage-specific and plastic human stem cell derivative, providing an engraftable human embryonic neuronal progenitor in high purity and large supply with adequate neurogenic potential for scale-up CNS regeneration as stem cell therapy to be translated to patients in clinical trials.  

Controlled by Financial Conflicts --- How Did CIRM Board Members Preempt Prop 71 Bond? Why Would Stem Cell Meetings Sponsored by CIRM Blacklist Human Embryonic Stem Cell Research?

Financial conflict of interest without transparency is the formula for abuse and government corruption that CIRM (California Institute for Regenerative Medicine), the California state stem cell agency, has. Anyone with slightest scientific integrity would be shocked to see ICOC such daring undertaken by financial conflicts on California stem cell report, not just a few millions, it is billions, it is hundreds of millions of government fund disappearing into CIRM board’s own institutions and companies without asking any questions if they have any scientific merits and if they have followed the legal procedure of Prop 71. How come Alan Trounson dared to claim that there is no evidence of financial conflicts of interest for CIRM awards on California stem cell report. Maybe Alan Trounson is at easy to know that he and CIRM have already set up many non-transparent safety precautions to cover up any evidences, e.g. use pre-application to deliberately select conflict of interest awards, never disclose any information of those pre-applications, and never allow investigator-initiated applications and appeals for pre-applications. Maybe Alan Trounson is at easy to know that he and CIRM have already preempted Prop 71 bond prior to ICOC public meetings, that no matter which award would come up, no matter who would appeal and win the appeal, the money would always go to CIRM board members’ institutions. Alan Trounson and CIRM have intentionally given California stem cell researchers many difficulties to even apply for CIRM funding by denying them the rights to apply for public fund by law, such as non-transparent pre-application procedures (see our previous posts) and conflict of interests RFAs (e.g., CIRM RFA 12-01, 12-02, 12-03, 12-04, 12-05) in which CIRM has specifically written that Prop 71 stem cell research is not allowed to apply (evidences if you’d like). If those safety precautions of CIRM to preempt Prop 71 bond prior to ICOC public meetings have failed, Alan Trounson even personally denied the existence of such grants. Alan Trounson’ comment on California stem cell report made self-contradicted presumption that university has better sciences or researchers, which is financial conflict of interest evidence itself. University of California, the biggest beneficiary of Prop 71 so far, has not been where the leadership and advances of stem cell research reside in, nor has shown any support to human embryonic stem cell (hESC) research, as evidenced by that UC officials secretly shut down UC hESC research labs. None of CIRM’s excuses to reject or not to consider human embryonic stem cell research grants of Prop 71 has applied to any ICOC awards. Capricor did not have a single piece of scientific data that their cells can become beating heart muscle as we did for human embryonic stem cells (hESCs), or their science or research is better. UC Davis did not have a single piece of scientific data that their cells can regenerate as we did for hESCs, or their science or research is better. STEM did not have a single piece of scientific data that their cells have the capacity/efficiency to repair as we did for hESCs, or their science or research is better. If it is not financial conflicts, we would like to know what it is that those ICOC board members were all awarded $ 20 Ms, while Prop 71 stem cell research could not even pass CIRM pre-application?

Like Alan Trounson said, there is no evidence for financial conflicts of interest. All ICOC board members have followed the symbolic public step to excuse themselves to vote on their own grants, to the extent that none of those ICOC board members’ awards had enough votes required by the law to approve the funding. But those ICOC board members still have their awards passed to receive Prop 71 bond anyway. Maybe we only need to dig little bit deeper for evidences, if take a look at those stem cell meetings keynoted by Alan Trounson or sponsored by CIRM along the courses, such as ISSCR (International society for stem cell research), world stem cell summit, and stem cell meetings on the mesa. How come almost all the invited speakers have preferably been selected by CIRM to receive $Ms of CIRM awards, even though their talks and research have nothing to do with Prop 71 stem cell research? How come none of these so-called stem cell meetings sponsored by CIRM would welcome hESC research, as evident by no hESC research of Prop 71 was ever invited to present. In our experience, hESC research is not only unwelcomed by stem cell meetings sponsored by CIRM, it is in fact, shockingly, on their blacklist. We all know that ISSCR has lobbied a big number of CIRM funding to sponsor their meetings, did ISSCR use those CIRM money to put human embryonic stem cell research on their blacklist? I might be naïve to feel shocked when my poster of hESC research (titled “deriving cardiac elements from pluripotent hESCs for heart reconstitution”) was declined to be presented by ISSCR program chair at 2010 ISSCR meeting in San Francisco when it was perfectly welcomed to be presented in other non-stem cell meetings (see ISSCR poster communications below at SDRMI wordpress). Why? After I emailed to question the fairness of the meeting committee in selecting scientific presentation and restate the importance of our hESC research to the stem cell field, ISSCR responded that my abstract of only 300 words was actually scored by ISSCR committee and it was found that 90% of the abstract restated a problem that everyone recognizes [referred to our openly concerns for the induced pluripotent stem cells (iPS cells)], and no results in the abstract [in fact, 25% of the abstract was devoted to state the results, though no one would put data/results, reflected in the title, in the abstract] (see ISSCR poster communications below at SDRMI wordpress). I was left without any words because I have never heard such thing that meeting committee would score the abstracts, and apparently, CIRM had also picked up ISSCR such financial conflict of interest tradition to score word and space limited pre-applications. I had emailed and called then ISSCR president Irving Weissman of Stanford University, incoming president Fred Gage of Salk Institute, treasure Sean Morrison, no one responded. We all heard talks of Larry Goldstein and some other members of ISSCR founder’s cycle on the stage that had virtually no stem cell research results to present, but they have never been declined by those meetings sponsored by CIRM. Today, restating those shocking financial conflict of interest results that Irving Weissman gave his personal favorite Shinya Yamanaka preferential keynote for iPS cells at the ISSCR meeting, Deepak Srivastava (the ISSCR program chair) of UCSF would receive big funding for iPS cells and heart reprogramming soon from NIH, and ironically, NIH would soon got sued; Irving Weissman gave his wife preferential on stage presentation for their own company, and Stem cell Inc’s adult stem cells of no Prop 71 scientific merits would get special treatment for $40 M from CIRM, let alone equal amount or more that Irving Weissman has already taken for himself from CIRM with virtually no results, I should feel quite lucky that they had not come after me to shut down my hESC research lab at that time.