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

Abstract

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.

NEL-Like Molecule-1 (Nell1) Is Regulated by Bone Morphogenetic Protein 9 (BMP9) and Potentiates BMP9-Induced Osteogenic Differentiation at the Expense of Adipogenesis in Mesenchymal Stem Cells

“…At least 15 different BMPs have been identified in humans, and disruptions in BMP signaling result in a variety of skeletal and extraskeletal anomalies differentiation [3,4,7]. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity of differentiating into osteoblastic, chondrogenic, and adipogenic lineages [8][9][10][11][12][13]. MSCs have attracted significant attention for their potential role in stem cell biology and regenerative medicine [12][13][14][15][16][17][18].…”

“…Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity of differentiating into osteoblastic, chondrogenic, and adipogenic lineages [8][9][10][11][12][13]. MSCs have attracted significant attention for their potential role in stem cell biology and regenerative medicine [12][13][14][15][16][17][18]. Through a comprehensive analysis of the 14 types of BMPs' osteogenic activities, we demonstrated that BMP9 is among the most osteogenic BMPs that induce osteoblastic differentiation of MSCs by regulating a distinct set of downstream mediators of osteogenic signaling [19][20][21][22][23][24][25][26][27], as well as through extensive crosstalk with other major signaling pathways [28][29][30][31][32][33][34][35].…”

Bone Morphogenetic Protein-9 Effectively Induces Osteo/Odontoblastic Differentiation of the Reversibly Immortalized Stem Cells of Dental Apical Papilla

“…Conventional mesenchymal stem cells (MSCs) are nonhematopoietic multipotent cells, which have the capacity to differentiate into osteoblastic, chondrogenic, and adipogenic lineages although MSCs have been shown to differentiate into other lineages [8][9][10]. Besides bone marrow, MSCs have been isolated from other tissues, including periosteum, brain, liver, bone marrow, adipose, skeletal muscle, amniotic fluid, and hair follicle lineages [9,10]. While MSCs isolated from various tissues share many similar characteristics, they exhibit discernible differences in their expression profile and differentiation potential [9].…”

Ligament Tissue Engineering Using a Novel Porous Polycaprolactone Fumarate Scaffold and Adipose Tissue-Derived Mesenchymal Stem Cells Grown in Platelet Lysate

“…[7][8][9][10][11] Utilizing both strategies is critical because manipulation of mesenchymal cell differentiation has shown promise in regeneration of native tissue. [12][13][14] Currently, there is considerable interest in defining ideal ligament scaffolds and therefore our goal has been to create a novel engineered neoligament tissue. In this study, we have examined growth of mesenchymal cells on a synthetic scaffold prepared from biodegradable polymers in the presence of ligament-related growth factors to assess whether such biologically enhanced scaffolds have the potential to restore native ligamentous tissue and architecture.…”