Minnesota sceptical of funding Human Embryonic Stem Cell Research

Among those handful of states that fund embryonic as well as other forms of stem cell research, Minnesota is the newcomer.[1]

Minnesota is home to the nation’s first interdisciplinary institute dedicated to stem cell research, the University of Minnesota Medical School’s Minnesota Stem Cell Institute, founded in 1999.  Even so, public funding for all forms of stem cell research there was approved only in 2014, with the first grants being made in 2015. This year’s grants mark the third round of funding.  Regenerative Medicine Minnesota (RMM) is charged with approving and distributing the grants.

By way of comparison, both California and Maryland began funding stem cell research in 2007.  More on this below.

In the three years that Minnesota has provided state funds for stem cell research, it has noticeably steered clear of funding human embryonic stem cell research (hESCR).

In 2015, the first round of grant making,  just under $3 million in grants was given to six research projects.

None of them involved hESCR.

In 2016, $2.75 million was distributed to 9 research projects.

Again, none of them utilized human embryonic stem cells (hESCs).

Ten grants were awarded in 2017, totaling just under $5 million.

Of the ten, nine explicitly funded non-embryonic stem cell research. The research description for the tenth one creates some ambiguity, as it refers to “pluripotent stem cells,” without specifying whether they are embryonic or non-embryonic.

Nine of the grants were clearly non-embryonic.  (Regarding the remaining grant, there is room for ambiguity.  The research description refers to “pluripotent stem cells” which could refer to non-embryonic iPSCs, as well as hESCs.)

As noted before on this blog (here, here, and here), California and Maryland have in recent years strongly favored research using adult, induced pluripotent and other forms of non-embryonic stem cell research in their grant making.

But this was not always the case.

When both states handed out their first grants in 2007, they strongly favored hESCR.  Maryland gave only 4 grants to projects using adult stem cells, while 11 projects using hESCR received grants – almost three times as many.

California first round of grants went to 72 research projects, all of them utilizing hESCs.  A second round of grants in 2007 went to 29 projects – again, all of them centered on hESCs (two also involved somatic cell nuclear transfer, a.k.a., cloning).

This has changed over the years, with both states now heavily favoring non-embryonic stem cell research in their grant making.

Minnesota, in marked contrast, has given little, if any, support for hESCR.  Why? Timing may provide an answer.

California and Maryland began funding stem cell research against a background of hype and hyperbole regarding the potential of hESCs to cure any number of diseases and conditions.  Human embryonic stem cells were hyped as the “gold standard” in the field of regenerative medicine, while adult stem cell research was dismissed as far inferior.

All that began to change in 2007, when Shinya Yamanaka discovered a method to produce what he called “induced pluripotent stem cells.”  Like embryonic stem cells, these cells were fully pluripotent.  However, they did not require the destruction of human embryos; they could be derived from a simple somatic cell, such as a skin cell.  With a ready source of ethically non-contentious, fully pluripotent stem cells now available, more and more researchers began turning to them rather than hESCs.

Moreover, adult stem cells were proving far more versatile and effective in providing therapeutic benefits to patients than those who dismissed them as inferior had predicted.  While not yet providing cures, patients treated with adult stem cells for such things as multiple sclerosis, spinal cord injury, diabetes and other diseases began to show improvements from their treatments. In fact, over 1 million patients have been treated thus far with adult stem cells.

When Minnesota handed out its first stem cell grants in 2015, the changes the advent of iPSCs had wrought in the field of regenerative medicine were evident.  Also evident by then was the complete failure of hESCR to live up to all the hype regarding miracle cures they were supposed to bring about.  Only a handful of clinical trials were underway using hESCs; in contrast, the NIH on its website listed thousands of clinical trials for patients using adult stem cells.[2]

It is thus not unreasonable to assume that given these developments, Minnesota decided to steer clear altogether of hESCR and instead provides funds for what has proven to be far more promising adult, induced pluripotent and other non-embryonic stem cell research.

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[1] The other states are California, Maryland, Connecticut and New York.

[2] At http://www.clinicaltrials.gov/ct2/results?term=adult+stem+cell+transplants&type=Intr
  A recent study has questioned the validity of at least 18 trials listed on the website.  That still leaves several thousand valid trials listed testing adult stem cells.

Another State Prefers Non-Embryonic Stem Cell Research

Maryland is one of a handful of states to publicly fund embryonic stem cell research.[1]  In 2006, the state established the Maryland Stem Cell Research Fund (MSCRF), which distributes grants to stem cell research projects.  The first round of grants was in 2007, and over the years the Fund has distributed millions of dollars to such research

It is also home to the Johns Hopkins School of Medicine, one of the nation’s most prominent centers of stem cell research.

Earlier this year, the MSCRF released its annual report for 2016.  The report lists 26 research programs funded last year amounting to over $8.2 million.  Fully 90% of the funds dispersed -- $7.7 million -- went to 22 projects using adult and other non-embryonic stem cell research.  Only one project to receive a grant used human embryonic stem cells (hESCs) exclusively (three used both hESCs and induced pluripotent stem cells, aka iPSCs).  That is a sea change from the first round of grants the MSCRF made in 2007.

As with other states that first chose to fund hESC research, Maryland did so in the wake of then-President George W. Bush’s 2001 decision to fund hESCR, but to limit such funding to hESC lines already in existence.  Some states chafed at such limits, and so decided to fund the research on their own, without such restrictions.  At the time, hESCs were being hailed by scientists, politicians, celebrities and other public figures as having the potential to cure any number of diseases and conditions – Alzheimer’s, Parkinson’s,  diabetes, heart failure and spinal cord injury, among many others.   Ethically non-contentious adult stem cell research, on the other hand, was characterized as inferior, capable at best of only limited use in providing therapeutic benefits to patients.

Thus, the grants distributed in 2007 by MSCRF reflected this belief.  Out of 24 grants, 11 went to projects using hESCS, or 45%.  Only 4 grants were given to research projects centering on adult stem cells.  The 11 hESC research projects received $5.2 million while the 4 adult stem cell projects received less than half that - a mere $2.4 million.

But over the years, this pattern began to shift, with an increasing share of grants going to non-embryonic stem cell research (such as adult and induced pluripotent stem cell research) and fewer to hESC research projects.

By 2010, this new pattern displayed a decisive turn away from hESCR and towards ethically non-contentious, non-embryonic stem cell research.  Funding for non-embryonic stem cell research outstripped funding for hESCR 10 to 1, with the former receiving $9.9 million and the latter just over $1 million.  This pattern will likely continue for as long as MSCRF continues to distribute grants, as those distributed in 2016 once again shows.

In the early years of the public policy debate over funding for hESCR, numerous researchers affiliated then and now with Johns Hopkins testified before Congress on the superiority of such research over all others to advance the goals of regenerative medicine and on the urgent need to expand federal funding for it.

Over the years, Maryland’s pattern of funding for stem cell research would seem to indicate that there has been a clear change of mind on this.  And Maryland is not alone on this -- as this blog has noted before (here, here, and here), California’s Institute for Regenerative Medicine – the nation’s largest funder of stem cell research outside the federal government  -- has also over the years shifted more and more of its grants to non-embryonic stem cell research as well.

These shifts in grant making by Maryland and California seem to indicate, at the very least, that hESCs can no longer be claimed as the “gold standard” for stem cell research and providing therapeutic benefits to patients.  That claim now belongs to research using ethically non-contentious, non-embryonic stem cells. 

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[1] The others are California, New York, Connecticut and Minnesota.

CIRM Sponsored Clinical Trial Program Notable for Near Lack of hESCs

The California Institute of Regenerative Medicine (CIRM) is nearing the end of its ten year term.  Debate in California is ongoing as to whether CIRM will actually close, or whether it will continue in a different form with different funding sources.

The Alpha Stem Cell Clinics Network program may very likely be one of the last major initiatives CIRM takes before its current term is over sometime this year.  As such, it is emblematic of the funding course CIRM has travelled over the years.

The Network’s goal, according to CIRM, “is to accelerate the development and delivery of stem cell treatments to patients.”  To do this, CIRM authorized the creation of up to 5 alpha clinics.  These clinics are to be set up at academic institutions across California in order to serve as a “hub for stem cell clinical trials.” So far, three such clinics have been established, housed at City of Hope, University of California/San Diego, and UCLA/UC Irvine.

Earlier this year, at City of Hope, the Network held its second annual symposium, where patients and doctors met to discuss ongoing research and review progress in clinical trials underway.

At the time the symposium was held, there were 36 CIRM-funded Alpha Stem Cell Network clinical trials underway, spread across the three already established alpha clinics.

This blog has called attention to the way that CIRM – founded to give priority funding to human embryonic stem cell research – has over the years been providing the lion’s share of its grants to adult and other non-embryonic stem cell research.

A look at the Alpha Stem Cell Network clinical trials shows the same pattern of funding that has come to characterize so many of CIRM’s grants: away from research using human embryonic stem cells (hESCs) in favor of research using adult and other non-embryonic stem cell alternatives.

Only two of the trials listed on CIRM’s website utilize hESCs. However, they are really the same trial, with two different phases, so out of the 36 ongoing alpha network trials, only one is using hESCs.  Moreover, although utilizing such cells, they are not even the main focus of the trial.[1]

The trial is being conducted by a company called ViaCyte.  ViaCyte is testing a device it is developing that is intended to be placed under a patient’s skin, in order to deliver pancreatic progenitor cells derived from hESCs.  So the focus of the study is the performance of the device, not the efficacy of the stem cells it delivers for treating diabetes.

But should the device prove to be successful, it could deliver non-embryonic derived stem cells useful for treating diabetes as well.

For example, Harvard researcher Doug Melton has produced identical sets of mature, insulin producing beta cells from both hESCs and non-embryonic, induced pluripotent stem cells.  So if a device such as Viacyte’s should prove successful in delivering cells, it could just as well deliver ethically non-contentious, non-embryonic derived cells capable of treating diabetes.[2]

In fact, Melton is himself working on his own version of such a device.  Moreover, Melton has expressed concern that because the cells being used by ViaCyte to test its device are embryonic-derived progenitor cells, not yet fully differentiated to produce insulin, the cells may take months to mature into true insulin producing cells.  He has also expressed concern that not all the progenitor cells will necessarily develop into insulin producing ones, but rather could develop into other types of pancreatic cells.  Thus, while the device itself may prove efficacious, the embryonic stem cell derived progenitor cells it is intended to deliver may be far less so. 

So as CIRM nears the completion of its original term, the grants it has made to the Alpha Clinic Stem Cell Network are again confirming that adult and other non-embryonic stem cells would appear to be showing the most promise for helping patients.

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[1] Eight of the trials used adult stem cells and three iPSCs.  Three used cells derived from fetal tissue, which are considered adult stem cells, but which raise their own ethical issues. The remaining trials are a mix consisting of the use of the patient’s own cells and gene therapy.

[2] In 1999, then-President Clinton’s National Bioethics Advisory Commission became the first such body to investigate the ethical issues surrounding human embryonic stem cell research.  NBAC made pursuit of the research conditional: harvesting “left-over” IVF embryos for stem cells “is justifiable only if no less morally problematic alternatives are available for advancing the research (at pg. 53).”  In this instance, it would seem there are indeed ethical alternatives to ViaCyte’s embryonic stem cell-derived progenitors.