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

BMbackupCirculating 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).

So there are at least 3 candidate repair mechanisms for BM derived adult stem cells: transdifferentiation, fusion, and paracrine factors. All these mechanisms can be valid, but that presumably depends on the targeted tissue or organ. When a BM cell happens to enter into different tissues from the circulation it faces with different environments triggering different answers. In biology it is extremely hard to find any general laws applying to most phenomena but it is not necessary.

One thought on “Bone marrow derived adult stem cells: which way to go?

Comments are closed.