Role of mesenchymal stem cells in osteoarthritis treatment

Abstract

SummaryAs the most common form of joint disorder, osteoarthritis (OA) imposes a tremendous burden on health care systems worldwide. Without effective cure, OA represents a unique opportunity for innovation in therapeutic development. In contrast to traditional treatments based on drugs, proteins, or antibodies, stem cells are poised to revolutionize medicine as they possess the capacity to replace and repair tissues and organs such as osteoarthritic joints. Among different types of stem cells, mesenchymal stem cells (MSCs) are of mesoderm origin and have been shown to generate cells for tissues of the mesoderm lineage, thus, raising the hope for them being used to treat diseases such as OA. However, given their ability to differentiate into other cell types, MSCs have also been tested in treating a myriad of conditions from diabetes to Parkinson's disease, apparently of the ectoderm and endoderm lineages. There are ongoing debates whether MSCs can differentiate into lineages outside of the mesoderm and consequently their effectiveness in treating conditions from the ectoderm and endoderm lineages. In this review, we discuss the developmental origin of MSCs, their differentiation potential and immunomodulatory effects, as well as their applications in treating OA. We suggest further investigations into new therapies or combination therapies that may provide more effective treatment for bone and joint diseases. Furthermore, cell-based therapy and its associated safety and effectiveness should be carefully evaluated before clinical translation. This review provides updated information on recent approval of clinical trials and related applications of MSCs, and discusses additional efforts on cell-based therapy for treating OA and other joint and bone diseases.

BMSCs‐Derived Exosomes Ameliorate Pain Via Abrogation of Aberrant Nerve Invasion in Subchondral Bone in Lumbar Facet Joint Osteoarthritis

“…Bone marrow mesenchymal stem cells (BMSCs) are pluripotent cells with the capability of self‐proliferation and multi‐differentiation . Much attention has been paid to their therapeutic efficacy in regenerative medicine, as BMSCs have proved to secrete neurotrophic cytokines and anti‐inflammatory molecules . Recent studies have demonstrated that a paracrine mechanism plays a pivotal role in the therapeutic effects for stem cell transplantation, which puts exosomes in the research hotspot .…”

“…13 Much attention has been paid to their therapeutic efficacy in regenerative medicine, as BMSCs have proved to secrete neurotrophic cytokines and anti-inflammatory molecules. 14,15 Recent studies have demonstrated that a paracrine mechanism plays a pivotal role in the therapeutic effects for stem cell transplantation, which puts exosomes in the research hotspot. 16 Exosomes are 40-150 nm in diameter extracellular vesicles originating from multivesicular bodies, such as stem cells and cerebrospinal fluid.…”

Current perspectives on biological approaches for osteoarthritis

“…As a result, a myriad of MSC delivery strategies have been developed over the last decade to enhance articular cartilage repair and, ultimately, to delay OA. Our understanding of MSCs for the treatment of OA has improved on the basis of preclinical animal models that have demonstrated reparative effects of MSCs for meniscus, cartilage, and bone repair . The therapeutic application of MSCs is in the early stage of clinical translation; however, for the field to develop further, standardized protocols for MSC banking and expansion need to be carefully considered before clinical translation .…”

“…Long‐term cultivation has been shown to reduce the differentiation potential and cause permanent morphological changes . Despite these limitations, there are a growing number of clinical trials testing MSCs for OA using different delivery approaches . The results generated from these studies may fulfill regulatory needs and demonstrate their safety and effectiveness …”

“…Our understanding of MSCs for the treatment of OA has improved on the basis of preclinical animal models that have demonstrated reparative effects of MSCs for meniscus, cartilage, and bone repair. 112,113 The therapeutic application of MSCs is in the early stage of clinical translation; however, for the field to develop further, standardized protocols for MSC banking and expansion need to be carefully considered before clinical translation. 114 In addition, low quantities of MSCs are isolated from bone marrow (BM MSCs), a common tissue source, and controlled in vitro expansion is necessary.…”