Cell-based therapy in the treatment of musculoskeletal diseases

Abstract

A limited number of tissues can spontaneously regenerate following injury, and even fewer can regenerate to a state comparable to mature, healthy adult tissue. Mesenchymal stem cells (MSCs) were first described in the 1960s-1970s by Friedenstein et al as a small population of bone marrow cells with osteogenic potential and abilities to differentiate into chondrocytes. In 1991, Arnold Caplan coined the term "mesenchymal cells" after identifying these cells as a theoretical precursor to bone, cartilage, tendon, ligament, marrow stroma, adipocyte, dermis, muscle, and connective tissues. MSCs are derived from periosteum, fat, and muscle. Another attractive property of MSCs is their immunoregulatory and regenerative properties, which result from crosstalk with their microenvironment and components of the innate immune system. Collectively, these properties make MSCs potentially attractive for various therapeutic purposes. MSCs offer potential in sports medicine, aiding in muscle recovery, meniscal tears, and tendon and ligament injuries. In joint disease, MSCs have the potential for chondrogenesis and reversing the effects of osteoarthritis. MSCs have also demonstrated potential application to the treatment of degenerative disc disease of the cervical, thoracic, and lumbar spine.

Keywords: immunomodulation; mesenchymal stem cells; musculoskeletal diseases; orthopedic surgery; regenerative medicine; tissue engineering.

Graphical Abstract

Figure 1.

MSC transplant increases callus size and changes callus morphology in fracture healing sites. (A) Depicts a μCT analysis performed 14 days after fracture calluses dissected from mice that received MSC transplant compared to controls with no transplant. Callous and new bone volume was calculated after subtracting the cortical bone volume from the total volume and the total bone tissue volume. ^#P < .05 versus no cells; ^##P < .01 versus no cells by Student’s t-test. No cells, n = 3; MSC, n = 6. (B) Three-dimensional reconstruction of whole calluses (B1, B2, B5, and B6) and sagittal sections (B3, B4, B7, and B8) were obtained 14 days after tibial fracture in calluses from mice that were transplanted with MSC or control untransplanted (no cells). Figure 1 and caption reprinted from Granero-Moltó et al. Copyright 2009 by Oxford University Press. Reprinted with permission.

Figure 2.

Changes in the WOMAC score during the 6‐month period after intra‐articular injection in the MSC group and control group of OA patients. Patients with injection of AD‐MSC showed significant improvement in the WOMAC score. Patients in the control group did not significantly change in the WOMAC score. (A) The WOMAC total score. (B) The pain subscore of the WOMAC. (C) The stiffness subscore of the WOMAC. (D) The physical function subscore of the WOMAC. Abbreviations: MSC, mesenchymal stem cell; WOMAC, Western Ontario and McMaster Universities Osteoarthritis index. Figure 2 and caption was reprinted from Lee et al. Copyright 2009 by Oxford University Press. Reprinted with permission.

Figure 3.

Torn meniscus before and after repair and transplantation of synovial MSCs. Arthroscopic images before and after repair and during transplantation of synovial MSCs, and tear & repair with suture threads (indicated by blue lines) graphics are shown. Figure 3 and caption reproduced from Sekiya et al. Copyright by Sage. Reprinted with permission.

Figure 4.

Change from baseline in tibiofemoral joint space width over 24 months (medical joint space width) following ACL reconstruction. (A) Change from baseline in tibiofemoral joint space width over 24 months (medial joint space width. (B) Mean and 95% CI shown. Abbreviations: HA, hyaluronan; MPC, mesenchymal precursor cells. Figure 4 reproduced from Wang et al. Copyright by BMC. Reproduced under Creative Commons Attribution (CC-BY) license.