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Bone Marrow Stem Cells

Bone Marrow (BM) is a potential source of stem cells for regenerative therapies. These cells are plastic and are able to “transdifferentiate” into tissue committed stem cells for other organs. The identification of primitive, very small, embryonic-like stem cells in BM supports the notion that this tissue contains a population of primitive stem cell, which, if transplanted was able to regenerate damaged tissues¹. Because of the experience of bone marrow transplantation in the treatment of hematological disorders, bone marrow–derived stem cells have also become a major tool in regenerative medicine.

The bone marrow harbors at least two distinct stem cell populations:

• HEMATOPOIETIC STEM CELLS (HSCS)
  Hematopoietic stem cells (HSCs) are multipotent stem cells that give rise to all the blood cell types including myeloid and lymphoid lineages. Cells can be obtained directly by removal from the hip using a needle and syringe, or from the blood following pretreatment with cytokines, such as G-CSF, that induces cells to be released from the bone marrow compartment.
  
  
• MESENCHYMAL STROMAL CELLS / MESENCHYMAL STEM CELLS
  Mesenchymal stem cells are progenitors of all connective tissue cells. These cells can be differentiated into bone, fat and cartilage.

Bone marrow (BM)-derived stem cells may be able to restore the functioning in damaged tissues through different mechanisms:

CELLULAR DIFFERENTIATION

Recently, it was reported that BMSCs are able to “transdifferentiate” or change commitment into cells that express early heart, skeletal muscle, neural, or liver cell markers.

PARACRINE EFFECT

The paracrine effect is brought about my stem cells in the following ways.

A. Increased angiogenesis
Stem cells produce local signaling molecules like VEGF, HGF and FGF2 that may improve perfusion and enhance angiogenesis to chronically ischemic tissue. They also promote autocrine self survival, resulting in improved end organ function.

B. Decreased inflammation
Stem cells appear to attenuate infarct tissue size and injury by modulating local inflammation when transplanted into injured tissue. Modulation of local tissue levels of pro-inflammatory cytokines by anti-inflammatory paracrine factors released by stem cells, are important in conferring improved outcome after stem cell therapy.

C. Anti-apoptotic and chemotactic signaling
MSCs appear to activate an antiapoptosis signaling system at the tissue damage border zone which effectively protects ischemia-threatened cell types from apoptosis. Furthermore, expression profiling of adult progenitor cells reveals characteristic expression of genes associated with enhanced DNA repair, upregulated anti-oxidant enzymes, and increased detoxifier systems.

D. Remodeling of the extracellular matrix
Stem cell transplantation alters the extracellular matrix, resulting in more favorable post-infarct remodeling, strengthening of the scar and prevention of deterioration in organ function. MSCs appear to achieve this improved function by increasing acutely the cellularity and decreasing production of extracellular matrix proteins.

E. Activation of neighboring resident stem cells
Finally, exogenous stem cell transplantation may activate neighboring resident tissue stem cells. These resident stem cells may possess growth factor receptors that can be activated to induce their migration and proliferation and promote both the restoration of dead tissue and the improved function in damaged tissue.

1. Hanna Sovalat et al, Identification and isolation from either adult human bone marrow or G – CSF - mobilized peripheral blood of CD34+/CD133+/CXCR4+/ Lin-CD45- cells, featuring morphological, molecular, and phenotypic characteristics of very small embryonic-like (VSEL) stem cells, Experimental Hematology, 2011;39(4):495-505