Premium
The Reparative Power of Multipotent Stromal Cells from Bone Marrow
Author(s) -
Prockop Darwin J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a37-a
Subject(s) - microbiology and biotechnology , mesenchymal stem cell , stem cell , progenitor cell , multipotent stem cell , stromal cell , adult stem cell , biology , stem cell transplantation for articular cartilage repair , bone marrow , clinical uses of mesenchymal stem cells , endothelial stem cell , immunology , cancer research , in vitro , biochemistry
Recent publications have demonstrated that most tissues contain stem‐like progenitor cells that play a key role in the repair of tissue injury. When the endogenous stem/progenitor cells in a tissue are exhausted, they are supplemented by similar stem/progenitor cells from the bone marrow. A major focus has been on the stem/progenitor cells from bone marrow referred to as mesenchymal stem cells or multipotent stromal cells (MSCs). MSCs and similar cells from other tissues have been shown to repair tissues by differentiating so as to replace injured cells, by producing chemokines, and in part by cell fusion. However, there has been no obvious explanation for repeated observations that MSCs enhance repair of tissues in experimental models in which their level of engraftment is extremely low. We have recently found that MSCs can repair injured cells and tissues by two additional mechanisms: Stimulation of the proliferation and differentiation of stem cells that are endogenous to a tissue and by transfer of mitochondria or mitochondrial DNA to cells with non‐functional mitochondria. Human MSCs infused into the hippocampus of immunodeficient mice stimulated proliferation of and neurogenesis by endogenous neural stem cells (Munoz et al. PNAS, 2005). Co‐culture of human MSCs with a line of pulmonary epithelial cells with non‐functional mitochondria generated clones of the epithelial cells with functional mitochondria as a result of active transfer of either mitochondria or mitochondrial DNA from the MSCs (Spees, Olson, et al., PNAS, 2006). More recently we observed (Lee et al., PNAS in press) that intravenously infused human MSCs lowered the blood sugar, increased mouse insulin and decreased morphological changes in the renal glomeruli of streptozocin‐treated diabetic mice (NOD/SCID). The human MSCs engrafted into the pancreas and increased both the number of islets and the immunoreactive mouse insulin per islet. The human MSCs also engrafted into the kidney but it was not apparent whether the decrease in renal pathology was explained by direct action of the cells or by the decrease in blood sugar. Therefore there are now multiple strategies for developing new therapies for a broad range of diseases by enhancing one or more of the multiple mechanisms whereby MSCs normally repair tissues. Supported in part by grants from NIH grants AR48323, HL 073755, HL075161, and HL073252; HCA the Healthcare Company, and the Louisiana Gene Therapy Research Consortium.