Feasibility Of Stem Cell Therapy Research Articles

BMP7 enhances the effect of BMSCs on extracellular matrix remodeling in a rabbit model of intervertebral disc degeneration

Intervertebral discs (IVDs) provide stability and flexibility to the spinal column; however, IVDs, and in particular the nucleus pulposus (NP), undergo a degenerative process characterized by changes in the disc extracellular matrix (ECM), decreased cell viability, and reduced synthesis of proteoglycan and type II collagen. Here, we investigated the efficacy and feasibility of stem cell therapy using bone marrow mesenchymal stem cells (BMSCs) over-expressing bone morphogenetic protein 7 (BMP7) to promote ECM remodeling of degenerated IVDs. Lentivirus-mediated BMP7 over-expression induced differentiation of BMSCs into an NP phenotype, as indicated by expression of the NP markers collagen type II, aggrecan, SOX9 and keratins 8 and 19, increased the content of glycosaminoglycan, and up-regulated β-1,3-glucuronosyl transferase 1, a regulator of chondroitin sulfate synthesis in NP cells. These effects were suppressed by Smad1 silencing, indicating that the effect of BMP7 on ECM remodeling was mediated by the Smad pathway. In vivo analysis in a rabbit model of disc degeneration showed that implantation of BMSCs over-expressing BMP7 promoted cell differentiation and proliferation in the NP, as well as their own survival, and these effects were mediated by the Smad pathway. The results of the present study indicate the beneficial effects of BMP7 on restoring ECM homeostasis in NP cells, and suggest potential strategies for improving cell therapy for the treatment of disc diseases.

Concise review: mesoangioblast and mesenchymal stem cell therapy for muscular dystrophy: progress, challenges, and future directions.

Mesenchymal stem cells (MSCs) and mesoangioblasts (MABs) are multipotent cells that differentiate into specialized cells of mesodermal origin, including skeletal muscle cells. Because of their potential to differentiate into the skeletal muscle lineage, these multipotent cells have been tested for their capacity to participate in regeneration of damaged skeletal muscle in animal models of muscular dystrophy. MSCs and MABs infiltrate dystrophic muscle from the circulation, engraft into host fibers, and bring with them proteins that replace the functions of those missing or truncated. The potential for systemic delivery of these cells increases the feasibility of stem cell therapy for the large numbers of affected skeletal muscles in patients with muscular dystrophy. The present review focused on the results of preclinical studies with MSCs and MABs in animal models of muscular dystrophy. The goals of the present report were to (a) summarize recent results, (b) compare the efficacy of MSCs and MABs derived from different tissues in restoration of protein expression and/or improvement in muscle function, and (c) discuss future directions for translating these discoveries to the clinic. In addition, although systemic delivery of MABs and MSCs is of great importance for reaching dystrophic muscles, the potential concerns related to this method of stem cell transplantation are discussed.

Stem cell engineering: limitation, alternatives, and insight

The 21st century will see improvements in the quality of human life. The development of new therapeutic technologies will prevent prevalent diseases and enable recovery from currently incurable diseases. The development of cell and tissue replacement therapies using stem cells and their progenitors will accelerate the development of causative treatments. The effort expended thus far in developing cell therapies has revealed many technical limitations. Thus, we must explore conceptual changes in the feasibility of stem cell therapy. This paper introduces the current limitations to stem cell engineering and ways to overcome these limitations, which will provide new insight into their clinical application.

Launching a clinical program of stem cell therapy for cardiovascular repair

Since the feasibility of stem cell therapy has been recognized, enthusiasm for this therapy has grown exponentially. Nevertheless, as professionals we must realize that this enthusiasm should relate not only to our scientific interest but also to the care of our patients. Within the next decade, patients' demand for the latest therapies is likely to rise because of changes in health care systems that will broaden availability. Stem cell therapy is likely to be among these in-demand treatments, and we must be prepared for this change. In this Review we discuss the basic principles of how to launch a clinical program for stem cell therapy for cardiovascular repair. First, we look at the composition of the program team. Second, we describe the different types of stem cells available in clinical practice. Third, we present in depth the two most widely applicable delivery approaches. Finally, we discuss selection of patients and approaches and clinical and imaging methods by which to evaluate the safety and efficacy of this therapy.

Bone Marrow Stem Cells for Myocardial Infarction

I’ll be back! — —Arnold Schwarzenegger When news broke in 2001 that bone marrow–derived stem cells (BMCs) regenerate cardiac myocytes after myocardial infarction (MI), the prospects of regenerative therapy suddenly dawned on the horizon of cardiovascular medicine. Along with reports about differentiation of BMCs into neurons, hepatocytes, and muscle,1–4 BMCs delivered to the heart were shown to transdifferentiate into cardiac myocytes and to rescue cardiac function after infarction.5,6 In fact, the initial reports by Anversa’s group,5,6 supported by numerous similar findings, spurred the translation of stem cell therapy into the clinical arena, although the cell isolation and delivery strategies for patients with acute MI differed considerably from the experimental procedures of direct myocardial injection. Indeed, a number of clinical trials now suggest not only safety and feasibility of stem cell therapy but also significant improvement of left ventricular function in patients with acute myocardial infarction.7–10 However, the ability of BMCs to transdifferentiate into cardiac myocytes has recently been questioned by various groups that failed to demonstrate permanent engraftment of transplanted BMCs in the infarcted heart. Because improvements in cardiac function were still noted despite the lack of myocyte transdifferentiation, alternate mechanisms of BMC action have been suggested to support cardiac recovery.11–13 Accompanying editorials questioned the methodological approach by Anversa’s group and the early translation of “controversial findings” into clinical trials.14 After all this heat, Anversa’s group was tuned “to be back” (like the Terminator). In this issue of Circulation Research , Kajstura et al15 add new fuel to the stem cell controversy. Supporting their initial observations, they not only provide evidence for extensive BMC transdifferentiation, but also present some evidence against a significant …

Stem cells and cardiovascular disease

Several recent discoveries have shifted the paradigm that there is no potential for myocardial regeneration and have fueled enthusiasm for a new frontier in the treatment of cardiovascular disease—stem cells. Fundamental to this emerging field is the cumulative evidence that adult bone marrow stem cells can differentiate into a wide variety of cell types, including cardiac myocytes and endothelial cells. This phenomenon has been termed stem cell plasticity and is the basis for the explosive recent interest in stem cell–based therapies. Directed to cardiovascular disease, stem cell therapy holds the promise of replacing lost heart muscle and enhancing cardiovascular revascularization. Early evidence of the feasibility of stem cell therapy for cardiovascular disease came from a series of animal experiments demonstrating that adult stem cells could become cardiac muscle cells (myogenesis) and participate in the formation of new blood vessels (angiogenesis and vasculogenesis) in the heart after myocardial infarction. These findings have been rapidly translated to ongoing human trials, but many questions remain. This review focuses on the use of adult bone marrow–derived stem cells for the treatment of ischemic cardiovascular disease and will contrast how far we have come in a short time with how far we still need to go before stem cell therapy becomes routine in cardiovascular medicine.