Recruitment and retention of human autologous CD34+ CD117+ CD133+ bone marrow stem cells to infarcted myocardium followed by directed vasculogenesis: Novel strategy for cardiac regeneration
Abstract
Ongoing clinical trials, in regenerative therapy of patients suffering from myocardial infarctions, rely primarily upon administration of bone marrow stem cells to the infarcted zones. Unfortunately, low retention of these cells, to the therapeutic delivery sites, reduces effectiveness of this strategy; thus it has been identified as the most critical problem for advancement of cardiac regenerative medicine.
Figure 1 Concept of novel strategy for cardiac regeneration with human autologous bone marrow cells. (A) Heterospecific, tetravalent antibodies (htAbs) contain binding domains for four different antigens: CD34, CD117, CD133, and myosin. They are injected into the solution flowing over the sarcomeres of the infarcted myocardium. (B) The htAbs dock onto myosins of the sarcomeres. Excess of the htAbs is cleared from the circulation. (C) Human, autologous, bone marrow stem cells (haBMSCs) are spiked into the solution. (D) The cells displaying on their surfaces CD34, CD117, CD133 are recruited and retained to the infarcted myocardium sarcomeres with the aid of the htAbs (only CD117 cell is shown here for clarity). The retained haBMSCs are directed to differentiate into endothelium with the defined factors (not shown).
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