ACT's Joint Venture SCRMI Reports in Prestigious Scientific Journal that Embryonic Stem Cells are a Potentially Unlimited Source of Functional Platelets for Transfusion

Ideal candidate for early clinical trials involving iPS cells

MARLBOROUGH, Mass.--(BUSINESS WIRE)--Jan 11, 2011 - Advanced Cell Technology, Inc. (OTCBB:ACTC) reported that its hemangioblast-based technology can be used to generate functional platelets from human embryonic stem cells (hESCs). The research, which appears online (published-ahead-of- print) in Cell Research ˆ’ a Nature Group journal ˆ’ by scientists at ACT's joint venture “Stem Cell & Regenerative Medicine International” (SCRMI) and colleagues at Harvard Medical School, Cha University, and the University of Illinois, shows that it is feasible to generate functional megakaryocytes and platelets from hESCs on a large scale. The hESC-platelets displayed features that were indistinguishable from those of normal blood platelets, and participated in clot formation and retraction in vitro. High-speed video microscopy showed that the platelets contributed to thrombi after vascular injury in mice, providing the first evidence for in vivo functionality of hESC-derived platelets.

Platelets play a critical role in stimulating clot formation and repair of vascular injury. However, due to their short storage time, there is constant demand for this life-saving blood component. Low platelet levels can occur in patients for a variety of reasons, including trauma, chemotherapy, radiation treatment, or organ transplant surgery. To circumvent risks associated with these conditions, platelet transfusions have become a mainstay therapy; yet high demand and limited shelf life have created a constant shortage in transfusion supplies. The ability to generate HLA-matched platelets in vitro would provide significant advantages over currently used donor-dependent programs.

“Unlike other sources of platelets,” said Robert Lanza, M.D., Chief Scientific Officer at ACT, and senior author of the study. “Human embryonic stem cells can be propagated indefinitely, providing a potentially unlimited and donorless source of cells for therapeutic purposes. This study shows that platelets can be produced from ES cells on a clinically relevant scale, and that they're functional upon transfusion into a living animal. The platelets displayed all of the structural and morphological criteria typical of blood platelets, and possessed characteristic properties of functional platelets such as activation by thrombin and formation of clots. Amazingly, they're even biconcave-shaped disks ˆ’ just like the real thing. Importantly, we demonstrated the platelets incorporated into thrombi (blood clots) in living mice in a manner similar to that observed for normal blood platelets. These results represent an important step towards generating an unlimited supply of platelets for transfusion. Since platelets contain no genetic material ˆ’ and can be irradiated before use ˆ’ they're ideal candidates for early clinical translation involving iPS cells.”

High clinical demand for donated platelets has stimulated interest in generating renewable sources of transfusable platelets. This paper reports a method that is amenable to large scale production efforts. “The system is exponentially more efficient in generating megakaryocytes than previous methods,” stated Shi-Jiang Lu, Ph.D., Senior Director of Stem International and co-senior author of the paper. “We have reduced dependence on animal serum and stroma, thus making the process more amenable to clinical translation. Thrombus formation in vivo is a rapid and highly dynamic process. It involves a large number of signaling pathways, enzymatic cascades, and the interplay of various protein components. By inducing natural platelet thrombus formation at the site of vascular injury in as little as 5-20 seconds, this system enabled us to monitor the real-time incorporation of the platelets into newly forming thrombi before they could be cleared from the microcirculation. We found that the hESC-derived platelets, like normal human blood platelets, incorporated into the developing mouse platelet thrombus through a platelet-specific mechanism.”

“More research is clearly needed before this technology can advance into the clinic,” stated Gary Rabin, Interim CEO and Chairman of ACT. “However, once this technology is perfected, we believe pluripotent stem cells ˆ’ both embryonic and iPS cells ˆ’ will play an important role in developing a renewable, donorless source of transfusable platelets.”

Other researchers on the paper include Jaehyung Cho (co-senior author) and Eunsil Hahm from the University of Illinois at Chicago; Feng Li, Hong Yin, Qiang Feng, Erin Kimbrel, and Wei Wang from Stem Cell & Regenerative Medicine International (SCRMI); and Jonathan Thon and Joseph Italiano at Children's Hospital, Brigham and Women's Hospital/Harvard Medical School.

Click here for a free copy of the paper: http://www.cell-research.com/index.asp

About Advanced Cell Technology, Inc.

Advanced Cell Technology, Inc. is a biotechnology company applying cellular technology in the field of regenerative medicine. For more information, visit http://www.advancedcell.com.

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Posted: January 2011

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