2 models of embryonic and adult blood formation: Figure by Ueno and Weissman

If you have previously thought (in your spare time) that the conventional wisdom concerning blood formation is that the yolk sac’s embryonic blood-forming cells serve only the embryo, while the source of adult blood-forming stem cells is the region called aorta-gonad-mesonephros (AGM), it’s time to think it again due the elegant experiments of Samokhalov et al.: Cell tracing shows the contribution of the yolk sac to adult haematopoiesis Nature 446, 1056-1061 (26 April 2007)

Legend: a, The ’separate’ model.

Bone marrow derived adult stem cells: which way to go?

Circulating bone marrow derived adult stem cells may serve as a backup rescue system if the pool of endogenous stem cells is exhausted (see cartoon). BM derived adult stem cells are the best characterized adult stem cells in humans (reviewed in Vieyra et al, 2005). The hematopoietic stem cell fraction of the bone marrow are capable of repopulating the entire blood system from the single-cell level. In addition, several studies demonstrated that multipotent bone marrow derived stem cells (BMDCs) differentiated into neural lineages and expressed specific markers for astrocytes, oligodendrocytes, neural precursors in the spinal cord, or migrated into the brain and expressed neuron-specific antigens (Mezey et al., 2000, Science, Koda et al., 2005, Neuroreport) One population of bone marrow derived cells, the mesenchymal stem cells or multipotent mesenchymal stromal cells are able to support hematopoiesis, and can also differentiate along mesenchymal and nonmesenchymal lineages in vitro (Keating, 2006, Curr Opin Hematol, Horwitz et al., 2007, Biol Blood Marrow Transplant). The multipotency in case of these primitive progenitor cells is the ability to generate cartilage, bone, muscle, tendon, ligament, and fat (reviewed in Oreffo et al., 2005, Stem Cell Rev). The suggested mechanism covers a series of asymmetrical divisions through which the originally undifferentiated progenitors start to express a new genetic pattern and eventually take the shape of a differentiated, functional cell in another tissue. The concept that lineage specific adult stem cells can change their fate, is called transdifferentiation. Recently, stem cell based regeneration in the heart (reviewed in Srivastava-Ivey, 2006, Nature) by transdifferentiation has been challenged and it was indicated that bone marrow derived mesenchymal stem cells do not transdifferentiate into hepatocytes (Murry et al, 2004, Nature). Instead it was suggested for the myocardium at least, that paracrine factors secreted by the bone marrow cells, like thymosin beta4 could be cardioprotective or angiogenic. (Gnecchi et al, 2006, Bock-Marquette et al 2004, Nature) The other basic and proposed regenerative mechanism is cell fusion between the transplanted cells and the damaged tissue cells (Nygren et al., 2004, Nat Med, Horvath et al., 2006, Neurosci Lett).

U.S. stem cell companies: a new roundup

From Investor’s Business Daily: Big pharmaceutical firms and major biotechs are holding back as well, William Caldwell CEO of Advanced Cell Technology says. “While all of them have stem cell development labs someplace in the bowels of their organizations, they are not putting capital into the sector.” These companies are nervous about the political and ethical climate associated with the science, he says. The same holds true for venture capital firms. “VCs will take any risks — except political,” Caldwell said. Despite the political fallout, there’s plenty of research going on. Plenty of companies are trying to turn the stem cell therapy business into a success.
StemCells, which develops therapeutics to treat damaged or deteriorating organ systems, has followed a path away from embryonic stem cells in developing a treatment for Batten’s disease, a rare genetic disorder in children that is always fatal. Using nonembryonic human stem cells, the firm is about to launch a phase one trial on six children. Targeting Batten’s might seem odd, considering that as few as 600 Americans suffer from the condition. But StemCells Chief Executive Martin McGlynn says doing so is the best way to make use of available money and leverage the technology into other diseases. The challenge is convincing others, including Wall Street, of the long-term payoff. A handful of firms are moving into various clinical-trial phases. Aastrom Biosciences is running a phase two trial of its bone repair technology based on adult stem cells. Osiris Therapeutics has a phase three trial of its stem cell drug for a life-threatening immune condition that can hit cancer patients after a bone marrow transplant. ViaCell is monitoring subjects who received its stem cell treatment for post-chemo-radiation blood cancer patients. The stem cells in the phase one trial came from umbilical cord blood.

Link

$16Million Israeli fund for anti leukemia treatment StemEx

$16-million round of financing goes for Gamida Cell to bring StemEx, a treatment for leukemia and lymphoma to the market. From Red Herring: The funds will be used to expand the Israeli stem cell startup’s pipeline and bring products to market. …The company reported extremely favorable clinical results from phase I and II studies of umbilical cord blood highly enriched with stem cells. If all goes well, the company plans to begin marketing StemEx in 2009 in partnership with Teva Pharmaceutical Industries, Israel’s largest drug company and an investor in Gamida Cell. Link

Crucial here is the cooperation of a stem cell biotech startup with a Big Pharma Giant. It is a whole new phenomenon.

Logo sources: Gamida, Teva.

Hematopoietic stem cell regulation: over the hedgehog?

Latest PNAS Early article by Stanford and McMaster researchers about the regulatory role of Hedgehog (Hh) signaling pathway in the balance between hematopoietic stem cell (HSC) homeostasis and regeneration in vivo. In brief: continued Hh activation during regeneration leads to HSC exhaustion. Link.