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| usnews |
One can now extend that impact phenomena analogy to the very pertinent research and translational effect Induced Pluripotent Stem Cell (iPSC) technology has had on the field of molecular biology and regenerative medicine.
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| Nature - Andy Potts |
It’s been ten years since Shinya Yamanaka and Kazutoshi Takahashi opened the portal to a whole new way of thinking and practicing the Art of Stem Cell Science by announcing that embryonic like properties could be regained in adult cells through molecular reprogramming.
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| Royal Society |
Much has been written about this apex moment of foundational innovation which ushered in the era of mainstream adoption of reverse engineering techniques on human cells but as we celebrate the ten year anniversary of iPSCs the opportunity presents itself to reflect and celebrate the coming age of Pluripotent science, specifically iPSCs.
Signals of Canada, a leading destination for "insiders’ perspectives on the world of regenerative medicine and stem cell research, written by scientists and professionals in the field" is hosting a "Blog Carnival" of which this article is one of a number being written covering the iPSC anniversary topic. Please click here to read what other bloggers think.
Inherently complex the various Pluripotent states and the multitude of their progressively differentiated descendants, as they relate to human biological microsystems, have only begun to be explored and understood. The inherent processes by which these interconnected derivative cells work and communicate are by and large just now being decoded and mapped. Although it’s been only ten years since the discovery of iPSCs and nearly 20 years since the human embryonic stem cells were first isolated the progress made to-date in translating Pluripotent science into real world clinical programs is very much the focus now of countless labs in the field, thanks in large part to the advent of “open source” iPSC technology. Prior to iPSCs the use of hESCs and the technology associated with its clinical translation was largely a specialty area limited in scope by funding, rules, regulations and IP. The advent of iPSCs changed that and with it the stem cell industry added a universal layer of potential. Whether it be using Pluripotent derived cells as tools or more notably to develop therapeutic cell candidates for clinical use those researching and developing applications using these cells are pioneering the way forward for the emerging era of next generation stem cell products.
To put not too fine a point on it, we have only scratched the surface and in the next ten years I expect there will be a number of Pluripotent treatments on the market in various countries and many many more still in the clinic moving towards approval with positive results over standard of care or filling-in where there is currently nothing to offer patients in need.
The topic of what can we expect to see on the frontline of the developing therapeutic market using Pluripotent derived cell products is often highlighted as a discussion point and rightly so given the limited public depth of awareness on the subject and the long standing promise by the sector as a potential basis for effective treatments.
Below are some of the targets and iPSC programs representative of the state of play in the field to look out for:
| TARGET - COMPANY/INSTITUTION - LEAD SCIENTIST(S) - CELL - DISEASE - AUTO/ALLO* | ||||||
| EYE | ||||||
| Riken/Healios | Masayo Takahashi | iRPE++ | Wet/Dry AMD++ | Auto>Allo | ||
| Notes: Program will address many disease states of Retina/Eye | ||||||
| Astellas RegMed | Lanza/MacLaren | iRNP++ | Dry AMD/RP++ | Allo | ||
| Notes: Program will address many disease states of Retina/Eye | ||||||
| UWisconsin Waisman | Gamm/Meyer | iRNP/RPE | Stargardt+ | Allo | ||
| Notes: Representative of next gen concept using eye "organoids" | ||||||
| NEI/CDI-Fuji | Bharti/Miller | iRPE | Dry AMD | Auto | ||
| Notes: US Govt backed program | ||||||
| Cedars Sinai/CIRM | Shaomei Wang | iRNP | RP | Allo | ||
| Notes: Advanced status w/ IND enabling studies | ||||||
| BRAIN | ||||||
| Kyoto Univ | Jun Takahashi | iNC | Pakinsons | Allo | ||
| Notes: Leading iPSC Parkinson program due to start in 2017 | ||||||
| Sloan Kettering | Lorenz Studer | eNC/iNC | Pakinsons | Allo | ||
| Notes: Top tier US hESC/iPSC lab moving to clinic | ||||||
| Scripps/CIRM | Jeanne Loring | iNC | Pakinsons | Auto | ||
| Notes: Bringing it home full circle w/ CIRM onboard | ||||||
| IMMUNE | ||||||
| Cynata | Slukvin/U Wisconsin | iMSC | GvHD++ | Allo | ||
| Notes: Entering clinic later in 2016 w/ solid pre-clinical data | ||||||
| Astellas RegMed | Robert Lanza | iMSC | Sepsis, Lupus++ | Allo | ||
| Notes: Multiple targets across board w/ pre-clinical hPSC data | ||||||
| BLOOD | ||||||
| Megakaryon-Kyoto/Tokyo+ | Eto/Nakauchi/Daley | iPlatelets | Cancer/Surgery++ | Allo | ||
| Notes: Leading Japanese program poised to enter clinic in 2017 | ||||||
| Novosang-Roslin/SNBTS++ | Marc Turner | iRBC | Thalassaemia++ | Allo | ||
| Notes: Leading UK Consortia looking to clinic in 2017 | ||||||
| Inserm/PlatOD | Dominique Baruch | iPlatelets | Cancer/Surgery++ | Allo | ||
| Notes: Leading French program nearing clinic in 2017 | ||||||
| Astellas RegMed | Robert Lanza | iPlatelets | Cancer/Surgery++ | Allo | ||
| Notes: Had a leading program using research grade iPSC line in 2013 | ||||||
| Players in CAR/Immuno Space | iBloodCells | Cancer/Immune | Auto>Allo | |||
| Notes: Auto/Allo B, T, NK, DC+ benefits 4 immuno product requirements | ||||||
*The above listing is representative of the sector and is not at all comprehensive. Apologies to the many great programs that should be there also.
hiPSC science has industry wide support globally and is a mainstream technology acceptable in jurisdictions in which other ES methods face challenges. Translational hurdles for hiPSC are specific to their reprogramming and to the adult to youthful conversion which forms the basis of the applied technology. This presents an additional safety component to the already strict regulatory oversight applied to the clinical translation of Pluripotent programs now and in the future.
hiPSC science has industry wide support globally and is a mainstream technology acceptable in jurisdictions in which other ES methods face challenges. Translational hurdles for hiPSC are specific to their reprogramming and to the adult to youthful conversion which forms the basis of the applied technology. This presents an additional safety component to the already strict regulatory oversight applied to the clinical translation of Pluripotent programs now and in the future.
Will they be highly successful and achieve revolutionary paradigm shifting status and establish new standards of care in their go-to-market quests?
That is a subjective question for each and every program and one which you could speculate on, yet it would be Hype to suggest definitively without established patient data. However, the indicative MOA and technology basis of those programs on the list point to a sound foundation to work from.
That is a subjective question for each and every program and one which you could speculate on, yet it would be Hype to suggest definitively without established patient data. However, the indicative MOA and technology basis of those programs on the list point to a sound foundation to work from.
In my opinion, Pluripotent science, specifically hiPSCs as a universal technology, has the very best chance to score across the board wins for the patient in areas of unmet medical needs.
Why?
Some of the reasons I have doggedly believed that lie in the very nature of the plasticity of the sources, youthful phenotypes, cell expression and innate modulatory properties. Other reasons specifically relate to the field’s capacity to precisely derive and modify them in-vitro while perfecting their required derivative purities and expandability to consistently replicate them indefinitely in volume under strict quality control for regulated mass market applications.
This potential, if successfully delivered together, will usher in a new Pluripotent Era in the Stem Cell Story.
Why?
Some of the reasons I have doggedly believed that lie in the very nature of the plasticity of the sources, youthful phenotypes, cell expression and innate modulatory properties. Other reasons specifically relate to the field’s capacity to precisely derive and modify them in-vitro while perfecting their required derivative purities and expandability to consistently replicate them indefinitely in volume under strict quality control for regulated mass market applications.
This potential, if successfully delivered together, will usher in a new Pluripotent Era in the Stem Cell Story.
Commentary
Are we at an inflection point?
Are we at an inflection point?
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| pavasoni |
Certainly the perceived slow pace of translational activities has been a media drag on the sector, irrespective of the actual comparative timelines to move from bench to bedside. In retrospect there are still only a surprisingly small number of clinical programs in trials worldwide using Pluripotent derived cells, due in large part to stricter preclinical and regulatory standards applied to safety issues associated with these cell sources. So one would say we’re definitely due some momentum building inflection points….
Human embryonic stem cell trials were initiated in the US some 6 years ago on the basis of only research cell lines after lengthy preclinical research and safety checks. Subsequent small studies in Europe and Korea using hESCs added additional safety data. These trials paved the way for iPSCs yet still today the only enrolled clinical trial for iPSC derived therapeutics is in Japan. This pioneering trial had been on hold for over a year as the cell source analysis flagged possible genetic instability issues and was switched out from an autologous approach to a recently approved allogeneic cell line and is due to resume in 2017. The one patient to-date receiving the iPSC based iRPE cell sheet for Wet AMD has been reported to be in good condition with no apparent safety issues associated with her procedure.
The rigorous standards of the need to use an NIH approved clinical grade cell line in the US has delayed the start of US trials on iPSCs and only just recently has one been announced as available. Pre-clinical lab work one would assume would now need to be done using that line for the clinical trial programs wishing to enter the clinic sometime in the future (yrs) or approval sought and granted for proprietary lines already used for clinical prep on existing developmental programs. This safety issue, albeit necessary and prudent, has forestalled the advancement of Western work and raised the bar from where hESCs entered the clinic.
When discussing timelines and where this segment of the sector is headed it’s important to factor in these types of regulatory hurdles one must overcome on the road to a Pluripotent IND, clinical trial approval and human phased testing. Trial design considerations require stringent oversight monitoring of Pluripotent trials and have and will slow down the translational best efforts of those academic and commercial players entering the space.
Generally if it takes longer that the average drug development process to see stem cell based products enter trials and progress through the Phases and a therapeutic emerge from any stem cell specific regulatory approval pathway people will continue to be disappointed. A scaled approach to the sector’s product entry and exit criteria seems reasonable given the variance of risks associated with different stem cell products under some form of adaptive umbrella.
Safety is of the essence and the nascent SC sector requires everyone err on the side of caution. This is the mantra I hear regularly and I can’t really say it’s not appropriate to a great extent. However, it is this writer’s opinion that the priority should not be overly weighted towards the slowest approach to protect the sector at the expense of patients willing to engage in regulated, open and comprehensive phase development programs designed to enroll and prove the science. Sufficient data can only be generated from a participatory system that is adaptive and accommodating not restrictive and burdensome by design or intent.
A Quad Pregnancy demands care & attention.
A Quad Pregnancy demands care & attention.
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| lifesitenews |
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| Ashley Gardner Quad IVF Reaction cnn |
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| buzzfeed |
To conclude I have reported on the stem cell industry, specifically the Pluripotent segment for many years, and it has been easily influenced by sentiment and competitive currents rather than sharpening its aim on achieving sector growth. What we all care about most are real solutions for the long list of conditions that continue to ail us and for those that we love. Rather than future technology leading, current programs built on the foundation of pioneering efforts in both the Adult and Pluripotent fields need to be clinically accessible and then successfully delivered widely. Supporting and driving all safe and effective stem cell solutions will propel the entire sector forward.
Safety with pace, open and inclusive. Driving patient centric solutions forward as a community, in a modernized regulatory environment, by design and for the people.
Advocacy for Cures.
Cheers
Refs:
Cell Press Nucleus - "iPSCs: A Decade of Discovery" (comprehensive review issue)
Cell Stem Cell Editorial: "10 Questions: Clinical Outlook for iPSCs" Cell Stem Cell, Vol 18, Issue 2, 170-173, DOI: 10.1016/j.stem.2016.01.023 (included in review issue ref above)
Ilic, D. and Ogilvie, C. (2016), "Human Embryonic Stem Cells — What Have We Done? What Are We Doing? Where Are We Going?". Stem Cells. doi:10.1002/stem.2450
The Niche, P.Knoepfler: "Yamanaka's baby turns 10 so here's a top 10 list of IPS cell hot button bullet points"
Refs:
Cell Press Nucleus - "iPSCs: A Decade of Discovery" (comprehensive review issue)
Cell Stem Cell Editorial: "10 Questions: Clinical Outlook for iPSCs" Cell Stem Cell, Vol 18, Issue 2, 170-173, DOI: 10.1016/j.stem.2016.01.023 (included in review issue ref above)
Ilic, D. and Ogilvie, C. (2016), "Human Embryonic Stem Cells — What Have We Done? What Are We Doing? Where Are We Going?". Stem Cells. doi:10.1002/stem.2450
The Niche, P.Knoepfler: "Yamanaka's baby turns 10 so here's a top 10 list of IPS cell hot button bullet points"
