scholarly journals Mesenchymal Progenitor Cells and Their Orthopedic Applications: Forging a Path towards Clinical Trials

2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
Deana S. Shenaq ◽  
Farbod Rastegar ◽  
Djuro Petkovic ◽  
Bing-Qiang Zhang ◽  
Bai-Cheng He ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Trials ◽  
Progenitor Cells ◽  
Therapeutic Potential ◽  
Donor Site ◽  
The United States ◽  
Bone Diseases ◽  
Mesenchymal Progenitor Cells ◽  
Differentiation Potential ◽  
Metabolic Bone Diseases

Mesenchymal progenitor cells (MPCs) are nonhematopoietic multipotent cells capable of differentiating into mesenchymal and nonmesenchymal lineages. While they can be isolated from various tissues, MPCs isolated from the bone marrow are best characterized. These cells represent a subset of bone marrow stromal cells (BMSCs) which, in addition to their differentiation potential, are critical in supporting proliferation and differentiation of hematopoietic cells. They are of clinical interest because they can be easily isolated from bone marrow aspirates and expanded in vitro with minimal donor site morbidity. The BMSCs are also capable of altering disease pathophysiology by secreting modulating factors in a paracrine manner. Thus, engineering such cells to maximize therapeutic potential has been the focus of cell/gene therapy to date. Here, we discuss the path towards the development of clinical trials utilizing BMSCs for orthopaedic applications. Specifically, we will review the use of BMSCs in repairing critical-sized defects, fracture nonunions, cartilage and tendon injuries, as well as in metabolic bone diseases and osteonecrosis. A review of www.ClinicalTrials.gov of the United States National Institute of Health was performed, and ongoing clinical trials will be discussed in addition to the sentinel preclinical studies that paved the way for human investigations.

scholarly journals The human arthritic hip joint is a source of mesenchymal progenitor cells (MPCs) with extensive multipotent differentiation potential

2020 ◽  
Author(s):  
Mike Wagenbrenner ◽  
Tizian Heinz ◽  
Konstantin Horas ◽  
Axel Jakuscheit ◽  
Joerg Arnholdt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Hip Joint ◽  
Collagen Type ◽  
Hyaline Cartilage ◽  
Joint Capsule ◽  
Mesenchymal Progenitor Cells ◽  
Differentiation Potential ◽  
Monolayer Cell

Abstract Background: While multiple in vitro studies examined mesenchymal progenitor cells (MPCs) derived from bone marrow or hyaline cartilage, there is little to no data about the presence of MPCs in the joint capsule or the ligamentum capitis femoris (LCF) of the hip joint. Therefore, this in vitro study examined the presence and compared the differentiation potential of MPCs isolated from the bone marrow, arthritic hyaline cartilage, the LCF and full-thickness samples of the anterior joint capsule of the hip joint. Methods: MPCs were isolated and multiplied in adherent monolayer cell culture. Osteogenesis and adipogenesis was induced in monolayer cell cultures for 21 days using a differentiation medium containing specific growth factors, while chondrogenesis in the presence of TGF-ß1 was performed using pellet-culture for 27 days. Control cultures were maintained for comparison over the same duration of time. The differentiation process was analyzed using histological and immunohistochemical stainings as well as semiquantitative RT-PCR for measuring the mean expression levels of tissue-specific genes.Results: This in vitro research showed that the isolated cells from all four donor tissues grew plastic adherent and showed similar adipogenic and osteogenic differentiation capacity as proven by the histological detection of lipid droplets or deposits of extracellular calcium and collagen type I. After 27 days of chondrogenesis proteoglycans accumulated in the differentiated MPC-pellets from all donor tissues. Immunohistochemical staining revealed vast amounts of collagen type II in all differentiated MPC-pellets, except for those from the LCF. Interestingly all differentiated MPCs still showed a clear increase in mean expression of adipogenic, osteogenic and chondrogenic marker genes. In addition the examination of an exemplary donor sample revealed that cells from all four donor tissues were clearly positive for the surface markers CD44, CD73, CD90 and CD105 by flow cytometric analysis.Conclusions: This study proved the presence of MPCs in all four examined donor tissues of the hip joint. No significant differences were observed during osteogenic or adipogenic differentiation depending on the source of MPCs used. Further research is necessary to fully determine the chondrogenic differentiation potential of MPCs isolated from the LCF and capsule tissue of the hip joint.

scholarly journals Isolation and characterization of bone marrow-derived mesenchymal progenitor cells with myogenic and neuronal properties

2007 ◽  
Vol 313 (5) ◽  
pp. 1008-1023 ◽  
Author(s):  
Mitsutaka Shiota ◽  
Toshio Heike ◽  
Munetada Haruyama ◽  
Shiro Baba ◽  
Atsunori Tsuchiya ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Mesenchymal Progenitor Cells ◽  
Isolation And Characterization

scholarly journals The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Naosuke Kamei ◽  
Kivanc Atesok ◽  
Mitsuo Ochi
Keyword(s):  
Bone Marrow ◽  
Clinical Trials ◽  
Endothelial Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Tissue Repair ◽  
Cell Populations ◽  
Neural Tissues ◽  
Cell Source ◽  
Stem Cell Populations

Endothelial progenitor cells (EPCs) derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regeneration in musculoskeletal and neural tissues including the bone, skeletal muscle, ligaments, spinal cord, and peripheral nerves. EPCs can be mobilized from bone marrow and recruited to injured tissue to contribute to neovascularization and tissue repair. In addition, EPCs or stem cell populations containing EPCs promote neovascularization and tissue repair through their differentiation to endothelial cells or tissue-specific cells, the upregulation of growth factors, and the induction and activation of endogenous stem cells. Human peripheral blood CD34(+) cells containing EPCs have been used in clinical trials of bone repair. Thus, EPCs are a promising cell source for the treatment of musculoskeletal and neural tissue injury.

Rat bone marrow derived mesenchymal progenitor cells support mouse ES cell growth and germ-like cell differentiation

2009 ◽  
Vol 33 (3) ◽  
pp. 434-441 ◽  
Author(s):  
Guanghui Cui ◽  
Zhengyu Qi ◽  
Xin Guo ◽  
Jie Qin ◽  
Yaoting Gui ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Differentiation ◽  
Cell Growth ◽  
Progenitor Cells ◽  
Es Cell ◽  
Mesenchymal Progenitor Cells ◽  
Rat Bone ◽  
Mouse Es Cell

scholarly journals The androgen receptor in bone marrow progenitor cells negatively regulates fat mass

2018 ◽  
Vol 237 (1) ◽  
pp. 15-27 ◽  
Author(s):  
Patricia K Russell ◽  
Salvatore Mangiafico ◽  
Barbara C Fam ◽  
Michele V Clarke ◽  
Evelyn S Marin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Androgen Receptor ◽  
Progenitor Cells ◽  
Fat Mass ◽  
Elevated Serum ◽  
Gene Replacement ◽  
Whole Body ◽  
Clinical Aspects ◽  
Mesenchymal Progenitor Cells

It is well established that testosterone negatively regulates fat mass in humans and mice; however, the mechanism by which testosterone exerts these effects is poorly understood. We and others have shown that deletion of the androgen receptor (AR) in male mice results in a phenotype that mimics the three key clinical aspects of hypogonadism in human males; increased fat mass and decreased bone and muscle mass. We now show that replacement of the Ar gene specifically in mesenchymal progenitor cells (PCs) residing in the bone marrow of Global-ARKO mice, in the absence of the AR in all other tissues (PC-AR Gene Replacements), completely attenuates their increased fat accumulation. Inguinal subcutaneous white adipose tissue and intra-abdominal retroperitoneal visceral adipose tissue depots in PC-AR Gene Replacement mice were 50–80% lower than wild-type (WT) and 75–90% lower than Global-ARKO controls at 12 weeks of age. The marked decrease in subcutaneous and visceral fat mass in PC-AR Gene Replacements was associated with an increase in the number of small adipocytes and a healthier metabolic profile compared to WT controls, characterised by normal serum leptin and elevated serum adiponectin levels. Euglycaemic/hyperinsulinaemic clamp studies reveal that the PC-AR Gene Replacement mice have improved whole-body insulin sensitivity with higher glucose infusion rates compared to WT mice and increased glucose uptake into subcutaneous and intra-abdominal fat. In conclusion, these data provide the first evidence for an action of androgens via the AR in mesenchymal bone marrow PCs to negatively regulate fat mass and improve metabolic function.

scholarly journals Modeling appendicular skeletal cartilage development with modified high-density micromass cultures of adult human bone marrow-derived mesenchymal progenitor cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Alessandro Pirosa ◽  
Karen L. Clark ◽  
Jian Tan ◽  
Shuting Yu ◽  
Yuanheng Yang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Culture System ◽  
Collagen Type ◽  
Micromass Culture ◽  
Type Ii ◽  
Collagen Type Ii ◽  
Mesenchymal Progenitor Cells ◽  
Environmental Toxicity ◽  
Gfp Reporter

Abstract Background Animal cell-based systems have been critical tools in understanding tissue development and physiology, but they are less successful in more practical tasks, such as predicting human toxicity to pharmacological or environmental factors, in which the congruence between in vitro and clinical outcomes lies on average between 50 and 60%. Emblematic of this problem is the high-density micromass culture of embryonic limb bud mesenchymal cells, derived from chick, mouse, or rat. While estimated predictive value of this model system in toxicological studies is relatively high, important failures prevent its use by international regulatory agencies for toxicity testing and policy development. A likely underlying reason for the poor predictive capacity of animal-based culture models is the small but significant physiological differences between species. This deficiency has inspired investigators to develop more organotypic, 3-dimensional culture system using human cells to model normal tissue development and physiology and assess pharmacological and environmental toxicity. Methods We have developed a modified, miniaturized micromass culture model using adult human bone marrow-derived mesenchymal progenitor cells (hBM-MPCs) that is amenable to moderate throughput and high content analysis to study chondrogenesis. The number of cells per culture was reduced, and a methacrylated gelatin (gelMA) overlay was incorporated to normalize the morphology of the cultures. Results These modified human cell-based micromass cultures demonstrated robust chondrogenesis, indicated by increased Alcian blue staining and immunodetectable production of collagen type II and aggrecan, and stage-specific chondrogenic gene expression. In addition, in cultures of hBM-MPCs transduced with a lentiviral collagen type II promoter-driven GFP reporter construct, levels of GFP reporter activity correlated well with changes in endogenous collagen type II transcript levels, indicating the feasibility of non-invasive monitoring of chondrogenesis. Conclusions The modified hBM-MPC micromass culture system described here represents a reproducible and controlled model for analyzing mechanisms of human skeletal development that may later be applied to pharmacological and environmental toxicity studies.

scholarly journals Identification of small juvenile stem cells in aged bone marrow and their therapeutic potential for repair of the ischemic heart

2013 ◽  
Vol 305 (9) ◽  
pp. H1354-H1362 ◽  
Author(s):  
Koichi Igura ◽  
Motoi Okada ◽  
Ha Won Kim ◽  
Muhammad Ashraf
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Therapeutic Potential ◽  
Left Ventricular ◽  
Stem Cell Markers ◽  
Differentiation Potential ◽  
Small Juvenile ◽  
Cardiomyogenic Differentiation ◽  
Proliferation And Differentiation

Stem cell-mediated cardiac regeneration is impaired with age. In this study, we identified a novel subpopulation of small juvenile stem cells (SJSCs) isolated from aged bone marrow-derived stem cells (BMSCs) with high proliferation and differentiation potential. SJSCs expressed mesenchymal stem cell markers, CD29+/CD44+/CD59+/CD90+, but were negative for CD45−/CD117− as examined by flow cytometry analysis. SJSCs showed higher proliferation, colony formation, and differentiation abilities compared with BMSCs. We also observed that SJSCs significantly expressed cardiac lineage markers (Gata-4 and myocyte-specific enhancer factor 2C) and pluripotency markers (octamer-binding transcription factor 4, sex-determining region Y box 2, stage-specific embryonic antigen 1, and Nanog) as well as antiaging factors such as telomerase reverse transcriptase and sirtuin 1. Interestingly, SJSCs either from young or aged animals showed significantly longer telomere length as well as lower senescence-associated β-galactosidase expression, suggesting that SJSCs possess antiaging properties, whereas aged BMSCs have limited potential for proliferation and differentiation. Furthermore, transplantation of aged SJSCs into the infarcted rat heart significantly reduced the infarction size and improved left ventricular function, whereas transplantation of aged BMSCs was less effective. Moreover, neovascularization as well as cardiomyogenic differentiation in the peri-infarcted area were significantly increased in the SJSC-transplanted group compared with the BMSC-transplated group, as evaluated by immunohistochemical analysis. Taken together, these findings demonstrate that SJSCs possess characteristics of antiaging, pluripotency, and high proliferation and differentiation rates, and, therefore, these cells offer great therapeutic potential for repair of the injured myocardium.

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