Adult Bone Marrow–Derived Cells for Cardiac Repair

Abstract

Background:The results from small clinical studies suggest that therapy with adult bone marrow (BM)derived cells (BMCs) reduces infarct size and improves left ventricular function and perfusion. However, the effects of BMC transplantation in patients with ischemic heart disease remains unclear.Methods: We searched MEDLINE, EMBASE, Science Citation Index, CINAHL (Cumulative Index to Nursing and Allied Health), and the Cochrane Central Register of Controlled Trials (CENTRAL) (through July 2006) for randomized controlled trials and cohort studies of BMC transplantation to treat ischemic heart disease. We conducted a random-effects meta-analysis across eligible studies measuring the same outcomes.Results: Eighteen studies (N = 999 patients) were eligible. The adult BMCs included BM mononuclear cells, BM mesenchymal stem cells, and BM-derived circulat-ing progenitor cells. Compared with controls, BMC transplantation improved left ventricular ejection fraction (pooled difference, 3.66%; 95% confidence interval [CI], 1.93% to 5.40%; PϽ.001); reduced infarct scar size (−5.49%; 95% CI, −9.10% to −1.88%; P=.003); and reduced left ventricular end-systolic volume (−4.80 mL; 95% CI, −8.20 to −1.41 mL; P=.006). Conclusions:The available evidence suggests that BMC transplantation is associated with modest improvements in physiologic and anatomic parameters in patients with both acute myocardial infarction and chronic ischemic heart disease, above and beyond conventional therapy. Therapy with BMCs seems safe. These results support conducting large randomized trials to evaluate the impact of BMC therapy vs the standard of care on patient-important outcomes.

CD45-CD14+CD34+ Murine Bone Marrow Low-Adherent Mesenchymal Primitive Cells Preserve Multilineage Differentiation Potential in Long-Term In Vitro Culture

“…Apart from the HSPC, which are wellcharacterized and the most abundant stem cells residing in the bone marrow, the non-hematopoietic compartment contains also neuronal and endothelial progenitors (Kabos et al, 2002;Quirici et al, 2001) as well as primitive cells exhibiting multilineage differentiation potential such as mesenchymal stem/stromal cells (MSC), multipotent adult progenitors cells (MAPC), marrow-isolated adult multilineage inducible cells (MIAMI) and very small embryonic-like stem cells (VSEL) (D'Ippolito et al, 2004;Jiang et al, 2002;Kucia et al, 2006;Pittenger et al, 1999). Recently, potential therapeutic applications of bone marrow-derived stem/primitive cells are extensively investigated in animal models as well as in patients with several types of diseases (Abdel-Latif et al, 2007;Dawn et al, 2008;Hofstetter et al, 2002;Houlihan and Newsome, 2008;Karussis et al, 2008;Lim et al, 2006;Matoba et al, 2008;Martin-Rendon et al, 2008;Torrente and Polli, 2008).…”

Controversial issue: Is it safe to employ mesenchymal stem cells in cell-based therapies?

“…Furthermore, application of MSC is thought to enhance hematopoietic stem cell engraftment in the course of bone marrow transplantation , to correct inherited disorders of bone and cartilage (Bolland et al, 2007), to ameliorate tissue damage after myocardial infarction (Abdel-Latif et al, 2007), and to treat graft-versus-host disease (Ringden et al, 2006). Also, attempts are being undertaken to employ MSC as a vehicle for gene therapy, e.g.…”

Cell Therapy for Diabetic Neuropathy

“…Overall, the emphasis must be placed on the idea that BM-MNCs induce neovascularization and improve manifestations of DN by their ability to promote angiogenesis. Also the safety of autologous BM-derived cells was reported by clinical trials [75].…”