Homing genes, cell therapy and stroke

Abstract

Stem cell therapies, such as bone marrow transplantation, are a promising strategy for the treatment of stroke. Bone marrow-derived stem cells (BMSCs) including both hematopoietic and mesenchymal stem cells (HSCs and MSCs) can exhibit tremendous cellular differentiation in numerous organs. BMSCs may also promote structural and functional repair in several organs such as the heart, liver, brain, and skeletal muscle via stem cell plasticity. Interestingly, ischemia is known to induce mobilization of BMSCs in both animal models and humans. The tissue injury is "sensed" by the stem cells and they migrate to the site of damage and undergo differentiation. The plasticity, differentiation, and migratory functions of BMSCs in a given tissue are dependent on the specific signals present in the local micro-environment of the damaged tissue. Therefore, the ischemic micro-environment has critical patho-biological functions that are essential for the seeding, expansion, survival, renewal, growth and differentiation of BMSCs in damaged brain remodeling. Recent studies have identified the specific molecular signals, such as SDF-1/CXCR4, required for the interaction of BMSCs and damaged host tissues. Understanding the exact molecular basis of stem cell plasticity in relation to local ischemic signals could offer new insights to permit better management of stroke and other ischemic disorders. The aim of this review is to summarize recent studies into how BMSCs reach, recognize, and function in cerebral ischemic tissues, with particular regard to phenotypical reprogramming of stem cells, or "stem cell plasticity".

Development of an allogeneic adherent stem cell therapy for treatment of ischemic stroke

“…Over the past decade, a number of different adult stem cell types have been isolated and subsequently tested in pre-clinical models of ischemic brain injury or stroke with encouraging results (Chen et al 2001a;Chen et al 2003b;Li and Chopp 2009;Ohtaki et al 2008;Shyu et al 2006;Yasuhara et al 2006b;Zhao et al 2002). Much of the early pre-clinical work performed by Chopp and colleagues used marrow derived stromal cells.…”

“…No cellbased therapeutics are currently on the market for treating stroke, which had an estimated cost of over $68.9 billion dollars to patients in both direct and indirect costs in the United States alone in 2009 (LloydJones et al 2009). Pre-clinical animal studies point to benefit derived from transplanted stem cells following ischemic injury in the CNS (Chen et al 2001c;Chen et al 2003b;Li and Chopp 2009;Ohtaki et al 2008;Shyu et al 2006;Yasuhara et al 2008;Yasuhara et al 2006b;Zhao et al 2002), in the heart (reviewed in (Charwat et al 2008;Ting et al 2008)), the peripheral vasculature (Aranguren et al 2008) and other inflammatory injury models (Aggarwal and Pittenger 2005;Kovacsovics-Bankowski et al 2008;Kovacsovics-Bankowski et al 2009). …”

Granulocyte-Colony Stimulating Factor Increases Donor Mesenchymal Stem Cells in Bone Marrow and Their Mobilization Into Peripheral Circulation but Does Not Repair Dystrophic Heart After Bone Marrow Transplantation

“…The prevalent hypothesis indicates that cardiac injury induces the generation of chemokines and cytokines, which mobilize stem cells from the BM to the site of myocardial injury. 19 The stem cells recruiting to the heart might undergo differentiation into cardiomyocytes and vascular cells in the cardiac niches and replace the injured myocardium. 20 Accordingly, we hypothesized that BMT from a healthy donor could become a causal therapy against hereditary cardiomyopathy by replacing hereditary disordered cardiac muscles with intact cardiomyocytes derived from donor BM stem cells.…”

Stromal cell–derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model

“…During the course of organ regeneration, however, it has been demonstrated that both local MSCs derived from the injured tissue and circulating MSCs collaborate in the healing of damaged organs. Circulating MSCs "sense" a tissue injury, migrate to the sites of damage, and undergo tissue-specific differentiation (11). However, the mechanisms responsible for MSC migration to the site of bone injury have not yet been revealed.…”