A focus shift is taking place in current adult stem cell biology. So far the two main candidate repair mechanisms for adult stem cells were transdifferentiation and fusion. The concept that lineage specific adult stem cells can change their fate, is called transdifferentiation (Mezey et al., 2000). 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. One population of bone marrow derived cells, the mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) (Prockop, Science) are able both to self-renew and differentiate into various cell types (cartilage, bone, muscle, tendon, ligament, and fat) in vitro and are present in many other tissues including fat, bone, skin, umbilical cord blood.(4)

Adult stem cells originally attracted attention because of the their stem cell-like properties, but the cells frequently repaired injured tissues and produced functional improvements without much evidence of either engrafment or differentiation. In transplantation trials the levels of donor MSCs detected in bone, skin and other tissues was less than 1% and it seemed probable that they are able to repair tissues in other and multiple ways too.

Impact:

• Future areas of research based mainly on Prockop DJ. Clin Pharmacol Ther. 2007 Sep;82(3):241-3.;

• Secreted cytokines and chemokines: 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);
• Stimulation of tissue stem/progenitors;
• Immunomodulatory effects of stem cells, anti-immune reactions: MSCs suppressed the mixed lymphocyte reaction in culture and shown to improve engraftment of bone marrow and graft versus host disease in patients (Le Blanc and Ringden, 2006);
• Anti-inflammatory effects of MSCs: suppression of inflammation;
• Mitochondrial transfer, in vitro: the transfer of mitochondria from hMSCs or fibroblast were able to rescue the aerobic respiration of respiration deficient cells in vitro (Spees et al, 2006).

Prockop DJ. "Stemness" does not explain the repair of many tissues by mesenchymal stem/multipotent stromal cells (MSCs).Clin Pharmacol Ther. 2007 Sep;82(3):241-3.
Spees JL, Olson SD, Whitney MJ, Prockop DJ. Mitochondrial transfer between cells can rescue aerobic respiration.
Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1283-8. Epub 2006 Jan 23.
Blog: Pimm: Bone marrow derived adult stem cells: which way to go? http://pimm.wordpress.com/2007/02/22/bone-marrow-derived-adult-stem-cells-which-way-to-go/