Kyoto Univ team eyes clinical test of platelets derived from iPS cells

A Kyoto University team plans to begin a clinical test using platelets grown from induced pluripotent stem cells to treat Aplastic anemia, a serious disease, sources with knowledge of the plan said Sunday.

The team led by professor Koji Eto is expected to begin the clinical test after getting approval from the Ministry of Health, Labor and Welfare. The university has already endorsed the plan.

Expectations are high in the field of regenerative medicine for iPS stem cells that can grow into any type of body tissue.

The world's first transplant of retinal cells grown from iPS cells into a patient has already been conducted and research is under way into the application of such cells to treat Parkinson's disease and heart failure.

So far, the team has established a method to produce high-quality platelets -- a key component of blood that can stem bleeding -- in large numbers through the use of iPS cells.

In the envisaged clinical test, the team plans to grow platelets from iPS cells from a patient. They will be injected into the patient to see the safety and effectiveness of the method, according to the sources.

Patients with Aplastic anemia are easy to bleed, get infections, and suffer from headaches as platelets and white blood cells decrease.

Patients with falling numbers of platelets are often treated with blood transfusions. But the patient in the upcoming clinical study has a special immune type and thus the use of platelets derived from the patient's own iPS cells can control rejection, the sources said.

Platelets are used in blood transfusions during surgery and to stem bleeding when people get injured.

Blood donations are one of the most useful ways to secure platelets for use in medical setting. But platelets can be used for a short period of time and ensuring stock is a challenge.

Source: Japan Today 

Japan Announces Physician-initiated clinical trials for Parkinson's disease using iPSCs

Kyoto University Hospital, in partnership with the Center for iPS Cell Research and Application (CiRA), Kyoto University, has planned physician-initiated clinical trials for Parkinson's disease that transplants dopaminergic progenitors1 generated from induced pluripotent stem (iPS) cells. The clinical trial notification was submitted to the Pharmaceutical and Medical Devices Agency (PMDA; the Japanese equivalent of the FDA) on June 4, 2018, and the clinical trials are scheduled to begin on August 1 this year.

Note: The candidate subjects are required to live in Japan, have Japanese public health insurance and can understand the Japanese informed consent form.

Outline of the Clinical Trials

1. Names

Selected patients will participate in both of the following clinical trials.

a) Kyoto Trial to Evaluate the Safety and Efficacy of iPSC-derived dopaminergic progenitors in the treatment of Parkinson's Disease (Phase I/II)

b) Kyoto Trial to Evaluate the Safety and Efficacy of Tacrolimus2 in the iPSC-based Therapy for Parkinson's Disease (Phase III)

2. Objectives

a) To evaluate the safety and efficacy of transplanting human iPS cell-derived dopaminergic progenitors into the putamen3 of Parkinson's disease patients.

b) To evaluate the safety and efficacy of using tacrolimus for Parkinson's disease patients who received transplantation of human iPS cell-derived dopaminergic progenitors into their putamen.

3. Strategy

Dopaminergic progenitors are generated from iPS cells prepared at the iPS Cell Stock for Regenerative Medicine4 at CiRA and then transplanted into the bilateral putamen of seven subjects (Parkinson's disease patients) at the Kyoto University Hospital. 

The source iPS cells were generated from third-party donor blood cells, meaning the transplantations will be allogeneic. Because of a possible transplant rejection, patients will receive a standard immunosuppressant, tacrolimus. Each subject will be observed for two years post transplantation.

4. The cell transplantation surgeryApproximately 5 million iPS cell-derived dopaminergic progenitors will be transplanted by stereotaxic brain surgery5 into the left and right sides of the patient's putamen. 

Glossary

1）Dopaminergic progenitorsDopaminergic neurons produce the neurotransmitter dopamine. In Parkinson's disease, these cells degenerate, resulting in decreased dopamine production. Dopaminergic progenitors differentiate into dopaminergic neurons. Animal studies have shown that transplanted progenitor cells will differentiate into mature dopaminergic neurons, resulting in efficient engraftment in the brain.

2）TacrolimusAn immunosuppressant commonly used following organ transplantation.

3）PutamenA region in the basal ganglia that is innervated by midbrain dopaminergic neurons.

4）iPS Cell Stock for Regenerative MedicineClinical-grade iPS cells are generated from healthy donors with specific cell types (HLA homozygosity) that are less likely to cause immune rejection in many people, and are stockpiled at CiRA following thorough quality check.

5）Stereotaxic brain surgeryThis neurosurgery involves drilling small holes on the patient's skull, through which a needle is entered or electrodes are embedded. One of the current therapies for Parkinson's disease, deep brain stimulation (DBS) surgery, is a type of the stereotaxic brain surgery.

Sources: CiRA PR 

Japan approves clinical trials of stem cell treatment for Parkinson's disease - Kyoto University to conduct first-ever iPS-based test for incurable disease

KYOTO (Kyodo) --  A Kyoto University research team said Monday it will begin this week a clinical test using induced pluripotent stem cells to treat Parkinson's disease, in what will be the world's first application of iPS to the progressive neurological disorder.

The team led by Jun Takahashi, a professor at the university's Center for iPS Cell Research and Application, has received government approval and is soliciting several patients to participate in the trial to be conducted at Kyoto University Hospital, according to sources close to the matter.

The team is scheduled to hold a press conference to explain the details of the clinical test later in the day.

Parkinson's disease reduces dopamine-producing neurons in the brain and results in tremors in the hands and feet, and stiffness in the body. While there are treatments to relieve the symptoms, there is currently no cure for the disease.

In the clinical test that will start on Wednesday, nerve cells derived from other people and stored at the university will be transplanted into the brains of patients to supplement damaged nerve cells.The team has already tested the process on monkeys in a preclinical study, in which the movement of the affected animals improved without seeing any tumors that could develop into cancer in the brain over a two-year observation period.

The clinical trial will be led by doctors who will determine the safety and effectiveness of the test.Among other clinical tests of iPS cells, the government-backed Riken institute conducted the world's first transplant of retinal cells grown from iPS cells to a patient suffering from a serious disease in 2014.

Osaka University is also planning a clinical test for treating heart failure by using a heart muscle cell sheet created from iPS cells.

Source: Nikkei Asian Review 

Channel News Asia Coverage of Pakinson's iPSC Trial Topic

The Coming of Age of Pluripotent Science & Musings on a Sonogram

usnews

One of the most memorable images I can recall on the effect of catalytic dynamics for me during these years of scientific curiosity was the explosive result of sperm enzyme successfully impacting a human egg - almost Big Bang like in all its microscopic potential.

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.

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.

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. 

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. 

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. 

Commentary

Are we at an inflection point?

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.

lifesitenews

Ashley Gardner Quad IVF Reaction cnn

When I recently scanned the Pluripotent sonogram I saw some Art where 4 heads appeared! Unlike our shock horror double take when 2 appeared in my wife’s scan, I was glad to see the 4 represented there, happily squished together and well. One seems to be growing bigger at the expense of a couple of the others but by and large it’s a Bridge Gang willing and able to take on the challenges when alive and kickin. I personally look forward to seeing them all born healthy and grow, in addition to their Olympic caliber Adult cousins. That would give us semi-oldies the best chance when it´s our turn to ask for help from those wise and experienced in the Jedi ways of healing. This is where Advocacy for Cures comes in. 

buzzfeed

Hope is a powerful force and will always be there for patients in need. Unfortunately the reality is that most next generation Pluripotent cell solutions are still a few steps away, if not more, for those that suffer. High science, low science, no science - too many people continue to be excluded, lack alternatives, suffer & die from disease. Stem Cell Science offers potential solutions and requires stakeholders to rally around programs and data that deliver real world results, even marginal benefits over existing options while awaiting more advanced solutions.

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"  

Science Validation & The Rising Sun

Strategy, survival, direction, competition and growth opportunities are but a few fundamental elements in the maze of everyday life all professionals must navigate - no more so than those on the leading edge of managing scientific innovation.

Being at the forefront of change often elicits backdraft currents and polarization of entrenched positions. This is natural and can be seen as a positive reinforcement of the high threshold one must strive to in order to achieve acceptance. A sort of quality assay if you will - one which is analogous to peer review in a business setting.

A lot has been written on the news of the Ocata/Astellas deal regarding the value calculation and little on the actual merits of Validation for Ocata’s science, the step forward in its development plan and the broader implications for the stem cell sector.

This writer has covered Ocata for a long time and can attest to the finer details of the saga that was its Survival and Vindication. A road which has seen its fair share of episodic highlights - perhaps too many.

One could speak at length and talk of the dedicated character of those involved with the science and the constant pressure within & on the company to prove itself in a demanding uncompromising field. One piece termed the company a “lightning rod” - the story has all the hallmarks.

The end of an era? Yes, perhaps it is in many ways. I prefer to see it as the close of the 2nd act in a 3 act structure, where the rain is falling and mingling with the tears.

Lost independence isn’t easy to come to grips with. However, moving on from being a small volatile publicly traded company, with all the influences that entails, to being housed within a protective and nurturing parental structure is a very positive outcome - for the programs and patients in need. 

It signifies so much with regard to the science and efforts to help define the standards of a new treatment methodology in medicine. 

The deal is a solid affirmation from established pharma that the stem cell therapeutic sector is worth banking on. This comes on the heels of other momentum building developments in the space and perhaps is indicative of a growth driven consolidation phase.

There are many worthwhile questions surrounding the announcement and events leading up to the decision to sell that remain, even after recent company disclosures, and one would look to those involved to address them for the record. Lock stock comes to mind?

There is a saying which is often spoken in Catalonia - “the sun always rises” and aims to reinforce and embrace the positive.

Cheers

Blood & The Search For A Universal Drug Delivery System

The doctrine that we are all equal under God applies in reality to the very Blood of humanity that runs through our veins. This was the shocking truth that changed an age old way of intellectual & class division. After millennia Science did that not faith. The fluid of life is an interchangeable commodity that drives the body and mind. A genetic brain unique to a person's cells is common enough to be of practical benefit. Donors of all types, colors and creeds can have some siphoned off and provided to those that need a refill. 

We accept the DNA of another to live on, with new Blood, without question and without any harm.

With 7.2 Billion humans on the planet you would think that we'd have enough of the Red stuff to go around. Think again. We don't even have enough fresh supplies to meet current demand, let alone future requirements based on the donation system. How can we expect this system to suddenly change to meet the forecasted demand when the population hits 10 Billion within a few decades and then 15 Billion a generation or two later?

Enter science, as usual, to solve the human evolutionary dilemma - Create it.

Not only is it possible to do so now, in inexhaustible volumes to satisfy all, but those cell products can and will be modified by the Scientists & Doctors of this 2nd Blood Revolution to deliver the needed solutions against the parasites, funguses, viruses, bacterias et al. that plague & kill daily in countless numbers.

Engineered weapons of the vascular system that naturally hone in and destroy invading pathogens.

The below provides a rough summary of how this is coming together from the perspective of ACTC and it's scientific colleagues.

Cheers

Phase 1 - Blastomere Derived Renewable Stem Cell Line
Phase 2a - Clinical Expansion & Banking of Hemangioblast Derived Megakaryocytes
Phase 2b - Engineered Variants for Drug Delivery Requirements
Phase 3a - Differentiation of Platelets, Red Blood Cells & Line Derivatives 
Phase 4a - Biocompatible Unit Preparation & Universal Distribution
Phase 4b - Locally Served Fresh Product via Bioreactor Automated Production

________________________________________

REFERENCES:

Cell Research Jan 2011 - "Platelets generated from human embryonic stem cells are functional in vitro and in the microcirculation of living mice" - SCRMI, Univ of Illinois Chicago, Cha Univ, Harvard / BWH & ACTC 

Blood July 2014 - "Platelet bioreactor-on-a-chip" - Harvard / BWH, Univ Colorado & Colorado School of Mines, McGill, ACTC

Vector - Boston Children's Hospital Blog March 2014 - "The Platelet Whisperers" 

MedCity News April 2014 - "Biochip mimics how the body produces platelets so they could be made in a lab"

NY Times May 2014 - "Young Blood May Hold Key to Reversing Aging"

UCSF July 2014 - "Key to Aging Immune System Is Discovered" 

Proceedings of the National Academy of Sciences of the USA, June 2014 - Whitehead Institute & MIT - "Engineered red blood cells as carriers for systemic delivery of a wide array of functional probes"

The Scientist Sept 2014 - "Next Generation: Blood-Cleansing Device" - (Engineered MBL Protein use example in fighting Sepsis - with cell engineering it can be done without dialysis)

Advanced Cell Technology's Scientific Advisory Board

Dr. Langer's Lab & Dr. Jensen's Lab of MIT

The Scientist July 2013 - "Narrow Straits - Transfecting molecules into cells is as easy as one, two, squeeze." 

Proceedings of the National Academy of Sciences of the USA, Feb 2013 - "A vector-free microfluidic platform for intracellular delivery"

R&D, July 2013 - "Researchers put squeeze on cells to deliver"

Dr. Daley's Lab - "Hematopoiesis Research" - HHMI / Children's Hospital Boston / Havard  & "CellNet" - Children's Hospital Boston / Havard / Boston Univ & iPS mRNA Tech

Daley / Children's Hospital Boston / Harvard Patent Families: 

Biomechanical Induction of Hematopoiesis
Inhibition and Enhancement of Reprogramming by Chromatin Modifying Enzymes
Methods for Enhancing Hematopoietic Progenitor Cell Engraftment 
Method to Produce Induced Pluripotent Stem (iPS) Cells from Non-Embryonic Human Cells 
Method of Enhancing Proliferation and/or Hematopoietic Differentiation of Stem Cells
________________________________________

Advanced Cell Technology's Patent Portfolio for the Blood Program:

INEXHAUSTIBLE SOURCE OF RENEWABLE STEM CELLS:

Blastomere Non-Destructive Human Embryonic Stem Cell Technology 

Blastomere Patent Family

5 Granted US Patents: 1, 2, 3, 4, 5

iPS/Reprogramming Renewable Stem Cell Derivation papers 1 & 2

iPS/Reprogramming Renewable Stem Cell Patent Family Portfolio: 1, 2 with examples A, B, C and SCNT Tech

EARLIEST YOUTHFUL BLOOD LINE POSSIBLE

HEMANGIO-COLONY FORMING CELLS - US Patent Granted & Patent Family 

HEMANGIO COLONY FORMING CELLS AND NON-ENGRAFTING HEMANGIO CELLS - App Pub March 2011 & Patent Family 

UNIQUE BLOOD LINE CELL PRODIGY DERIVATION:

(WO2011069127) LARGE SCALE GENERATION OF FUNCTIONAL MEGAKARYOCYTES AND PLATELETS FROM HUMAN EMBRYONIC 
STEM CELLS UNDER STROMAL-FREE CONDITIONS - PCT Pub June 2011 & US App Pub Dec 2012 & Patent Family  
(Note: SCRMI is a JV between ACTC & Cha Biotech of Korea - North American Rights belong to ACTC - Japan/Korea to Cha - ROW split)

(WO2014100779) METHODS FOR PRODUCTION OF PLATELETS FROM PLURIPOTENT STEM CELLS AND COMPOSITIONS THEREOF - PCT Pub June 2014 & US App Pub Sept 2014