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.

First differentiated cell types in mammals are…

…blood cells, “generated in early-stage embryos, for instance in mice in the yolk sac at embryonic day (E) 7.0.-7.5, just 2 or 3 days after the undifferentiated conceptus implants in the uterus.” Source: Ueno-Weissman: Blood lines from embryo to adult Nature 446, 996-997 (26 April 2007)

Functional blood vessels from hESCs durable for at least 151 days

A really pushing-the-limits paper published by the Scadden lab as a Brief Communication in Nature Biotechnology Advance Online, just like the De Coppi, Atala et al. paper on human amniotic stem cells in January. This time human embryonic stem (hES) cells were differentiated into endothelial cells using a scalable step-by-step two-dimensional method, avoiding the formation of three-dimensional (3D) embryoid bodies from the cells and the inefficient spontaneous differentiation. The selected culture cells were labeled with enhanced green fluorescent protein (EGFP) to track their in vivo life after transplantation into immunodeficient (SCID) mice (see the green visualization on the picture). The differentiated cells were able to form functional blood vessels in vivo and “contributed to arborized blood vessels that integrated into the host circulatory system and served as blood conduits for 150 d”. Zack Z Wang, Patrick Au, Tong Chen, Ying Shao, Laurence M Daheron, Hao Bai, Melanie Arzigian, Dai Fukumura, Rakesh K Jain & David T Scadden: Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo

Significance: Scalability in tissue engineering,

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).

Virgin’s Branson and stem cell banking

BBC News: “Virgin founder Richard Branson is set to launch a company which will let families bank and store stem cells from their child’s umbilical cord.” Question: Why just umbilical cord blood cells, why not amniotic fluid derived stem cells, or amniotic placental stem cells which have a far more wider regenerative potential than cord blood cells according to recent studies?

Update: Nature News info: “There is, however, an issue regarding how long the cells can be stored — so far, the record for a successful transplant is eleven years after initial freezing in liquid nitrogen. Colin McGuckin, Professor of Regenerative Medicine at Newcastle University in the UK, notes that this may be a barrier to long-term use. “This is completely uncharted territory — we can’t say whether samples will or will not be useful.”“

$2.9 million NIH Quantum Grant for Neuro-Vascular Regeneration to help stroke patients

For the first time Quantum Grant goes for international research initiative to regenerate damaged brain cells and blood vessels for the treatment of stroke which occurs when an artery in the brain is blocked. The three-year, $2.9 million grant, funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), part of the NIH, will support research on neuro-vascular regeneration, which will make new brain tissues in the laboratory. The new brain tissue is planned to have its own blood supply to allow it to be placed into the damaged brains of stroke patients where it will provide a source of neural and vascular cells that will continue to develop and differentiate, repairing the injured tissue in the process. Main participants are: Karen Hirschi, deputy director of the Stem Cell and Regenerative Medicine Center within the Center for Cell and Gene Therapy at Baylor College of Medicine, Jennifer West of Rice University, Department of Bioengineering, Robin Lovell-Badge, head of the division of developmental genetics at the National Institute for Medical Research in London. Link

So this will mainly be a tissue engineering approach for brain regeneration, that is growing implantable brain tissue in vitro in a bioreactor with working blood vessels in it, which needs the combination of more then 2 differentiated cell types. Hard task. My questions: What kind of stem or progenitor cells will be the sources of neural cells? What is the planned volume of the tissue constructs? What type of neurosurgery is needed for a successful implantation?

Image source