Cell-Based Therapies for Degenerative Musculoskeletal Diseases

Abstract

Degenerative musculoskeletal diseases (DMDs), including osteoporosis, osteoarthritis, degenerative disc disease, and sarcopenia, present major challenges in the aging population. Patients with DMDs present with pain, functional decline, and reduced exercise tolerance, which result in long-term or permanent deficits in their ability to perform daily activities. Current strategies for dealing with this cluster of diseases focus on relieving pain, but they have a limited capacity to repair function or regenerate tissue. Cell-based therapies have attracted considerable attention in recent years owing to their unique mechanisms of action and remarkable effects on regeneration. In this review, current experimental attempts to use cell-based therapies for DMDs are highlighted, and the modes of action of different cell types and their derivatives, such as exosomes, are generalized. In addition, the latest findings from state-of-the-art clinical trials are reviewed, approaches to improve the efficiency of cell-based therapies are summarized, and unresolved questions and potential future research directions for the translation of cell-based therapies are identified.

Keywords: cell-based therapies; degenerative musculoskeletal diseases; exosomes; extracellular vesicles; stem cells.

Figure 1

Different types of cells and their derivatives are used in the treatment of DMDs.

Figure 2

Mechanisms of cell‐based therapy. A) Stem cells differentiate or replace specific cells. B) Stem cells produce various growth factors that exert trophic functions. C) Stem cells play an immunomodulatory role by exerting biological effects on various types of immune cells through cytokines in a non‐contact manner or through membrane‐bound molecules in a contact manner. D) Exosomes from stem cells play a regulatory role as mediators of intercellular communication.

Figure 3

Types of 3D cell culture systems. A) Liquid overlay. B) Cells aggregate at the bottom tips of drops. C) Suspension bioreactor. D) Scaffold‐based technique.