Treatment of osteonecrosis of the femoral head by core decompression and implantation of fully functional ex vivo-expanded bone marrow-derived mesenchymal stem cells: a proof-of-concept study.

Background: Based on several attributes involved in bone formation, bone marrow-resident mesenchymal stem cells (MSCs) have been employed in the treatment of patients suffering from femoral head osteonecrosis. Due to the low content of MSCs in the bone marrow, ex vivo expansion procedures are utilized to increase the cell number. Customarily, before administration of the resulting expanded cell product MSCs to the patient, its cellular identity is usually evaluated according to a set of "minimal phenotypic" markers, which are not modified by ex vivo processing.

Comparative study of the neural differentiation capacity of mesenchymal stromal cells from different tissue sources: An approach for their use in neural regeneration therapies.

Mesenchymal stem cells (MSCs) can trans/differentiate to neural precursors and/or mature neurons and promote neuroprotection and neurogenesis. The above could greatly benefit neurodegenerative disorders as well as in the treatment of post-traumatic and hereditary diseases of the central nervous system (CNS). In order to attain an ideal source of adult MSCs for the treatment of CNS diseases, adipose tissue, bone marrow, skin and umbilical cord derived MSCs were isolated and studied to explore differences with regard to neural differentiation capacity.

Mesenchymal stem cell therapy in the treatment of hip osteoarthritis.

This study was performed to investigate the safety and efficacy of the intra-articular infusion of expanded autologous bone marrow-derived mesenchymal stem cells (BM-MSC) to a cohort of patients with articular cartilage defects in the hip. The above rationale is sustained by the notion that MSCs express a chondrocyte differential potential and produce extracellular matrix molecules as well as regulatory signals, that may well contribute to cure the function of the damaged hip joint. A cohort of 10 patients with functional and radiological evidences of hip osteoarthritis, either in one or both legs, was included in the study.

Cell Therapy and Tissue Engineering Approaches for Cartilage Repair and/or Regeneration.

Articular cartilage injuries caused by traumatic, mechanical and/or by progressive degeneration result in pain, swelling, subsequent loss of joint function and finally osteoarthritis. Due to the peculiar structure of the tissue (no blood supply), chondrocytes, the unique cellular phenotype in cartilage, receive their nutrition through diffusion from the synovial fluid and this limits their intrinsic capacity for healing. The first cellular avenue explored for cartilage repair involved the in situ transplantation of isolated chondrocytes.

Mesenchymal stem cell therapy for the treatment of amyotrophic lateral sclerosis: signals for hope?

Based on the distinctive cellular, molecular and immunomodulatory traits of mesenchymal stem cells (MSC), it has been postulated that these cells may play a critical role in regenerative medicine. In addition to the participation of MSC in the repair of mesodermal-derived tissues (bone, cartilage), robust data have suggested that MSC may also play a reparative role in conditions involving damage of cells of ectodermal origin. The above content has been supported by the capability of MSC to differentiate into neuron-like cells as well as by a competence to generate a 'neuroprotective' environment.

Presence of osteoclast precursor cells during ex vivo expansion of bone marrow-derived mesenchymal stem cells for autologous use in cell therapy.

Background Aims: To obtain a cell product competent for clinical use in terms of cell dose and biologic properties, bone marrow-derived mesenchymal stem cells (MSCs) must be expanded ex vivo.

Methods: A retrospective analysis was performed of records of 76 autologous MSC products used in phase I or II clinical studies performed in a cohort of cardiovascular patients. In all cases, native MSCs present in patient bone marrow aspirates were separated and expanded ex vivo.

Mesenchymal stem cells and the treatment of conditions and diseases: the less glittering side of a conspicuous stem cell for basic research.

Not too long ago, several motivated and forward-looking articles were published describing the cellular and molecular properties of mesenchymal stem cells (MSCs), specially highlighting their potential for self-renewal, commitment, differentiation, and maturation into specific mesoderm-derived lineages. A very influential publication of that period entitled "Mesenchymal stem cells: No longer second class marrow citizens" [1] raised the point of view that "…challenges to harness MSC cell therapy to treat diseases … need to wait for the full comprehension that marrow is a rich source of mesenchyme-derived cells whose potential is still far from fully appreciated." Whether or not the prophecy of Gerson was fulfilled, in the last 8 years it has become evident that infusing MSCs into patients suffering a variety of disorders represents a viable option for medical treatment.

Therapeutic angiogenesis in patients with severe limb ischemia by transplantation of a combination stem cell product.

Objective: Angiogenesis involves the interplay of endothelial progenitor cells, pericytes, growth factors, and cellular matrix components. The use of mesenchymal stem cells, which are closely related to pericytes and produce diverse angiogenic growth factors and matrix molecules, seems to be a promising therapeutic modality. We postulate that the use of a combination cell product (mesenchymal stem cells in conjunction with a source of endothelial progenitor cells) is safe and efficient and may optimize the clinical results obtained with the use of endothelial progenitor cells alone.

Vascular disease and stem cell therapies.

Introduction And Background: Peripheral vascular disease is the leading cause of limb ischemia (LI). LI is manifested by claudication, ischemic rest pain, ulcers or gangrene. It is the result of peripheral arterial disease due to atherosclerosis.

Myocardial implantation of a combination stem cell product by using a transendocardial MYOSTAR injection catheter: A technical assessment.

Aim: Different types of progenitor cells have been used to improve cardiac conditions after myocardial infarction (MI). Results have shown that while the infusion of a single cell type is safe and feasible, efficacy is modest. Recently, the use of a combination, rather than a single, stem cell product has emerged as an attractive option to improve cardiac outcome after a MI.

Combination stem cell therapy for the treatment of medically refractory coronary ischemia: a Phase I study.

Purpose: Infusion of a source of endothelial progenitor cells (EPC) into the ischemic myocardium is emerging as a promising therapy for coronary ischemia, probably mediated by the formation of new blood vessels. Studies have shown that while the procedure is safe and feasible, efficacy results are contentious. The investigators hypothesized that the infusion of a combination cell product consisting of a source of EPC and mesenchymal stem cells (MSC) is safe and promotes the formation of more stable and mature blood vessels resulting in improved clinical outcomes.

Intracoronary infusion of a combination of bone marrow-derived stem cells in dogs.

Background: Infusion of diverse types of bone marrow cells, as a source of endothelial progenitor cells (EPCs), into the ischemic myocardium is emerging as a promising therapy for coronary ischemia, probably mediated by the formation of new blood vessels. Studies have shown that while the procedure is safe and feasible, efficacy results are contentious. The investigators in the present preclinical translation study hypothesized that the infusion of a combination cell product consisting of EPCs and other cell types, such as mesenchymal stem cells, promotes the formation of more stable and mature blood vessels resulting in improved clinical outcomes.

Combination stem cell therapy for the treatment of severe limb ischemia: safety and efficacy analysis.

The infusion of a source of endothelial progenitors (EPCs) to limb ischemia (LB) patients has been used to increase angiogenesis. Because the formation of new blood vessels involves, in addition to EPCs, other cells and angiogenic regulators, we postulate that a combination cell therapy including EPCs and mesenchymal stem cells (a source of pericytes progenitors and angiogenic regulators) may represent a preferential stimuli for the development of blood vessels. In this phase I clinical trial, patients with LI were infused with a cell product consisting of autologous bone marrow-derived mononuclear and mesenchymal stem cells.

Bone marrow-derived stem/progenitor cells: their use in clinical studies for the treatment of myocardial infarction.

Over the last six years, several centres around the world have started clinical trials to investigate the utilisation of bone marrow-derived cells for myocardial infarction. Different types and numbers of cells have been used assuming they possess a potential to originate new endothelial cells and/or cardiomyocytes to repair/regenerate the ailed heart. Despite diversity in number, clinical status of subjects, route of cell administration, and criteria to evaluate efficacy, the main conclusion drawn from these clinical studies was that such therapies were safe.

Adult hippocampus derived soluble factors induce a neuronal-like phenotype in mesenchymal stem cells.

Bone marrow-derived mesenchymal stem cells (MSCs) are not restricted in their differentiation fate to cells of the mesenchymal lineage. They acquire a neural phenotype in vitro and in vivo after transplantation in the central nervous system. Here we investigated whether soluble factors derived from different brain regions are sufficient to induce a neuronal phenotype in MSCs.

Mesenchymal stem cells and the treatment of cardiac disease.

The ischemia-induced death of cardiomyocytes results in scar formation and reduced contractility of the ventricle. Several preclinical and clinical studies have supported the notion that cell therapy may be used for cardiac regeneration. Most attempts for cardiomyoplasty have considered the bone marrow as the source of the "repair stem cell(s)," assuming that the hematopoietic stem cell can do the work.

Nonstimulated human uncommitted mesenchymal stem cells express cell markers of mesenchymal and neural lineages.

Ex vivo cultures of human bone marrow-derived mesenchymal stem cells (MSCs) contain subsets of progenitors exhibiting dissimilar properties. One of these subsets comprises uncommitted progenitors displaying distinctive features, such as morphology, a quiescent condition, growth factor production, and restricted tissue biodistribution after transplantation. In this study, we assessed the competence of these cells to express, in the absence of differentiation stimuli, markers of mesoderm and ectodermic (neural) cell lineages.

Marrow-derived mesenchymal stem cells: role in epithelial tumor cell determination.

Marrow stroma represents an advantageous environment for development of micrometastatic cells. Within the cellular structure of marrow stroma, mesenchymal stem cells (MSC) have been postulated as an interacting target for disseminated cancer cells. The studies reported here were performed to gain more information on the interaction of the human breast cancer cell line MCF-7 with human bone marrow-derived MSC cells and to investigate whether this interaction affects tumor cell properties.

Signals from damaged but not undamaged skeletal muscle induce myogenic differentiation of rat bone-marrow-derived mesenchymal stem cells.

The regenerative capacity of skeletal muscle has been usually attributed to resident satellite cells, which, upon activation by local or distant stimuli, initiate a myogenic differentiation program. Although recent studies have revealed that bone-marrow-derived progenitor cells may also participate in regenerative myogenesis, the signals and mechanisms involved in this process have not been elucidated. This study was designed to investigate whether signals from injured rat skeletal muscle were competent to induce a program of myogenic differentiation in expanded cultures of rat bone-marrow-derived mesenchymal stem cells (MSC).

Dynamic of distribution of human bone marrow-derived mesenchymal stem cells after transplantation into adult unconditioned mice.

Background: The use of mesenchymal stem cells (MSC) for cell therapy relies on their capacity to engraft and survive long-term in the appropriate target tissue(s). Animal models have demonstrated that the syngeneic or xenogeneic transplantation of MSC results in donor engraftment into the bone marrow and other tissues of conditioned recipients. However, there are no reliable data showing the fate of human MSC infused into conditioned or unconditioned adult recipients.

Subcellular distribution and mitogenic effect of basic fibroblast growth factor in mesenchymal uncommitted stem cells.

Uncommitted mesenchymal stem cells (MSC), upon commitment and differentiation give rise to several mature mesenchymal lineages. Although the involvement of specific growth factors, including FGF2, in the development of committed MSC is known, the effect of FGF2 on uncommitted progenitors remains unclear. We have analyzed on a comparative basis, the subcellular distribution and mitogenic effect of FGF2 in committed and uncommitted MSC prepared from human bone marrow.

Human cord blood-derived mesenchymal stem cells home and survive in the marrow of immunodeficient mice after systemic infusion.

Bone marrow is the residence site of mesenchymal stem cells (MSC), which upon commitment and maturation develop into several mesenchymal phenotypes. Recently, we have described the presence of MSC in human cord blood (cbMSC) and informed that their properties are the same as those for MSC obtained from adult bone marrow. In this study we have investigated the capability of transplanted cbMSC to home and survive in the marrow of unconditioned nude mice.

Gp130 activation by soluble interleukin-6 receptor/interleukin-6 enhances osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells.

Interleukin-6 (IL-6) promotes osteodifferentiation in bone-located progenitors; however, it is not known whether this cytokine affects the differentiation of bone marrow-located osteoprogenitors. To address this issue, we prepared human bone marrow-derived mesenchymal stem cells (MSCs), which were characterized by a cell surface phenotype and multipotential nature. It was observed that in the presence of IL-6, MSCs were not differentiated into the osteogenic lineage, as evidenced by a failure to induce alkaline phosphatase activity, an earlier marker of osteodifferentiation.