Thursday, 18 August 2016 15:40

The History of ADRC Technology Development

The Recent History of ADRC Technology Development The Recent History of ADRC Technology Development
The existence of Mesenchymal Stem Cells (MSC´s) has been known since the early 70ties after the discovery by Friedenstein and colleagues and the following description and research work done by Arnold Caplan, who was instrumental in describing the achieved knowledge of MSC´s sourced from Bone Marrow. 
At the turn of the Century the same took place for MSC´s sourced from Adipose Tissue (i.e. fat) and that discovery must have taken place either at Pittsburgh University or at UCLA- there is no consensus on this point. 

What is sure- is that long before that time- in the early nineties, when Isner et al discovered  the Endothelial Progenitor Cell (EPC) in blood (and marrow), which led to a lot of exitement in pursuing clinics in improving the human vasculature (mainly cardiac studies)- also a scientist by the name of Stuart Williams (see image below) discovered endothelial cells in fat, with exactly the same purpose in mind- repairing blood vessels.  He- however- missed the existence of MSCs for some reason, which are very abundant in Adipose Tissue.

Stuart WilliamsAlthough a popular article which appeared in Wired Magazine tells differently, I basically assume that Marc Hedrick, now CEO of Cytori Therapeutics together with Adam Katz and the Spaniard Ramon Llull were the major discoverers (there are others named too) of the MSC´s and MSC progenitors in adipose tissue when cleaned of resident adipocytes i.e. the real fat cells. At least the major patents of describing stromal cells and the way to extract them with collagenase etc, carry their names. 
The popular article from Wired Magazine should be quoted also, since here- most credit is given to Min Zhu, presently (still) Chief Scientist at Cytori-

A postdoctoral fellow named Min Zhu had become bored with the rheumatology research she was doing and was looking for a new field. She joined Hedrick's lab at UCLA in spring of 1999, and he set her to the task of finding out once and for all whether there were stem cells in fat.

Determining the qualities of a stem cell (versus a regular one) requires proving that it can differentiate into many cells, but Zhu hit a brick wall even before she could attempt that: After she isolated candidate stem cells from fat, the things refused to grow, let alone differentiate. Her wired1breakthrough came when she figured out that rather than using the standard fibroblasts as feeder cells in her culture, she would use blood. 

"She just brute-forced it," Hedrick says. "She was forging her own trail—with a machete." Using blood to nourish and grow the stem cells, Zhu managed to induce them to differentiate into three lineages: first bone and cartilage, then muscle, and then neuron. She walked into Hedrick's office and said, "I think I have something." In April 2001, the scientists published in the journal Tissue Engineering their discovery that adipose tissue is chock-full of stem cells. 

That last statement certainly was correct and the very first peer reviewed paper coming out on the science of fat cells was  "Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based Therapies", which stated Patricia Zuk and Min Zhu as main authors and the Pittsburgh based scientists Katz and Futrell as co-authors and Hedrick, Huang, Mizuno, Benhaim and Hedrick as UCLA based co-authors.  One year later the highly quoted paper "Human Adipose Tissue Is a Source of Multipotent Stem Cells" was published. This paper is highly referenced and the more popular of the two -as of August 2016 it has been cited 864 times in peer reviewed publications. Possibly also, since it is a free PMC article. Both papers you can download in the download section at the bottom of the page. For this paper- the Pittsburgh co-authors were replaced by other UCLA scientists. 

From the - let´s say, co-invention, between the University of Pittsburgh and UCLA- two commercial off-springs resulted. First, in 2001 - Artecel Sciences was founded, which Company received the Pittsburgh patent license and StemSource in 2002 received the same from the Regents of UC. 

drgimbleArtecel was based in Durham NC, where it was financed by Toucan Capital, led by Linda Powers, now CEO of Northwestern Therapeutics and recruited its scientific talent from Duke University, led by Jeffrey Gimble (image) who as we speak in 2016, still plays a major role in the advancement of ADRC science, until 2010 as Pennington Biochemical RC researcher, but since that time again as co-founder of LaCell Inc, since Artecel soon was just a paper Company which fought the 231 patent battle, won and still holds those rights.

As most of my readers know, StemSource founded by Hedrick and Katz in 2002, soon was taken over by MacroPore Biosciences, which Company changed it´s name to Cytori Therapeutics in 2005. What happened there, you can read in all its "glory" (warning: being cynical) at my other site- cytx-investor.com.
Although the beginning years were rather quiet and the "explosion" of research really started in earnest beyond 2010, some groups and universities have been leading research and development of the technology in a special way, which I should mention and which should be documented-


First, let´s say the orthopedic group, MOVE, at the Vrije Universiteit of Amsterdam, first led by Professor Wuisman, who however died a premature death and who´s task was taken over by Marco Helder, who contributed with his colleagues quite a lot in the bone growth area. Recently they reported on the first clinical trial in humans, which results were quite impressive.

Second, the group in Tulane, Louisiana, where hundreds of pigs were sacrificed for the ADRC science by Professor Eckhart Alt and his country fellowmen, Kai Pinkernell, to prove the superior impact of ADRCs in the cardiac setting. Their work was taken over at a later point in time by Bruce Bunnell, who is researching in the neurological arena and has been President of IFATS, whilst hosting the IFATS meeting in New Orleans in 2015. 

And last but not least- let´s say- all Frence contributors to the science- be they the Toulouse group led by Louis Casteilla and Anne Bouloumie, who did a lot to advance basic science and did feasibility work on PAD, or be they the Marseille group led by Guy Magalon, without whom,  Cytori Therapeutics probably would not exist today. Keywords- diffuse scleroderma.

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