Joint and Bone: From Bench to Bedside

By Ahmed El-Hashash

Joint and Bone: From Bench to Bedside, Volume Three, the latest release in the Stem Cell Innovation in Health and Disease series, is a timely and fascinating collection of information and new discoveries that provides a contemporary snapshot album from the fast-moving field of regenerative medicine and stem cell therapeutics. This new volume addresses the molecular players underlying iPSC formation, maintenance, and expansion and differentiation, bringing chapters that describe cutting-edge research for understanding stem cell functions in joint and bone diseases, and for developing methods to bring stem cells from bench to bedside.

Each chapter includes insights ranging from the use of mouse and human organoid cultures, genetic editing in vitro and in vivo, and human iPSCs to study stem cell functions and model joint and bone diseases.

• Provides cutting-edge research needed to understand stem cell functions in joint and bone diseases
• Develops processes to bring stem cells from bench to bedside
• Includes up-to-date references on stem cell biology and function in the joint and bone

• Language: English
• Publisher: Academic Press
• Release date: Jan 30, 2023
• ISBN: 9780323983303

Book preview

Introduction

Deming Jiang¹,² ¹Innovation Center for Smart Medical Technologies & Devices, Binjiang Institute of Zhejiang University, Hangzhou, P.R. China ²Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou, P.R. China

Many disorders affect the bones and joints, ranging from traumatic bone fractures to chronic arthritis. If patients are not treated properly, chronic pain and disability will afflict them both physically and mentally. Healthy joints (such as knees, ankles, shoulders, wrists, and finger joints) and bones (such as the femur and humerus) allow the human body to move with ease.

Bones have many vital functions and contribute to human health. Bones can protect the fragile organs (such as the brain), exert hematopoietic function, maintain electrolyte balance (such as calcium), and regulate blood glucose levels by releasing osteocalcin (Grabowski, 2009). As bones participate in many details in human health, bone diseases can destroy normal life. Among different bone diseases, symptoms and treatment strategies are varied. Osteoporosis is one of the most prevalent bone disorders which leads to bone loss and susceptibility to fracture (Wang et al., 2021). Metabolic bone disorders caused by mineral or vitamin deficiencies is a big contributor to osteoporosis and other related diseases such as osteomalacia and Paget disease (Di Rocco et al., 2019). Fracture is another common bone disease occurs in any age-group. Children are more likely to have wrist fracture while older adults have more fragile hips.

A joint is made up of two or more bones meeting to allow movement. There is a lot of overlap between bone diseases and joint diseases. If joints develop diseases, bones are susceptible to implicative damage (i.e., arthritis). Arthritis is a leading cause of disability worldwide which will involve about 80 million US adults by 2040. Common joint disorders include osteoarthritis, rheumatoid arthritis, spondyloarthritis, juvenile idiopathic arthritis, lupus, gout, and bursitis.

Although many medicines have been developed to treat bone and joint disorders, most of them cannot cure the diseases. For rheumatoid arthritis, traditional drugs (i.e., methotrexate and sulfasalazine) can slow disease progression and novel antiinflammatory agents (i.e., adalimumab and etanercept) were developed (Burmester and Pope, 2017; van Vollenhoven, 2009). Meanwhile, surgical replacement of hips and knees, rather than drug treatment, is much more frequent (Sarzi-Puttini et al., 2005). For osteoporosis, bisphosphonates (i.e., alendronate and risedronate) are mainly used for treatment (Tu et al., 2018).

Recent advances in stem cell research have prompted the development of cell-based therapies for bone and joint diseases and disease models for investigating pathogenesis mechanisms. Stem cells have the ability to self-renew and differentiate into cells derived from all three germ layers. Progenitor cells are defined by restricted abilities to self-renew and differentiate potential, such as mesenchymal stem cells (MSCs) and hematopoietic stem cells (Alison et al., 2002). Stem cells can differentiate into multiple tissues, including bone, cartilage, fat, and other tissues of the skeletal system, making them a promising candidate for clinical application. For example, patients who experience a nonunion fracture can benefit from stem cell therapy (Undale et al., 2009). For normal fracture, MSCs can proliferate and differentiate into chondrocytes and osteoblasts under the regulation of bone morphogenetic proteins and other factors, leading to bone healing (Tseng et al., 2008). As some patients fail to heal properly and develop nonunion, stem cell therapy for nonunion fracture has received considerable attention. For example, bone marrow–derived osteoprogenitor cells were expanded, combined to porous hydroxyapatite scaffolds in vitro, and implanted for curing four patients with diaphyseal segmental defects (Quarto et al., 2001; Marcacci et al., 2007). Transplantation of stem cells has also been applied for treating osteogenesis imperfecta (Horwitz et al., 1999), hypophosphatasia (Whyte et al., 2003), osteoarthritis (Lu et al., 2019), and other bone and joint diseases.

For understanding the pathogenesis mechanism and developing new therapeutics for bone and joint diseases, establishing accurate and tractable disease models is essential. Although transgenic animals or transformed cell lines have been well established, they are difficult to simulate the physiology of patients and explain why many drug candidates are inefficient (Sterneckert et al., 2014). Patient-specific stem cells are useful to form bone and joint disease models due to the limitless self-renewal and differentiation properties. Stem cells can be easily expanded in vitro for basic research and drug discovery. Recently, genome editing is used to genetically modify patient-derived stem cells for studying genetically complex disorders. In addition, the rapid advancement of organoid technology allows new insights into disease initiation and opens new avenues for disease modeling and new drug discovery.

The stem cell technology has demonstrated its potential to identify new therapies and provide a greater understanding of bone and joint disease. The innovation of stem cell–related research and techniques can boost confidence in overcoming those chronic bone and joint diseases.

References

Alison et al., 2002 Alison MR, Poulsom R, Forbes S, Wright NA. An introduction to stem cells. The Journal of Pathology. 2002;197(4):419–423.

Burmester and Pope, 2017 Burmester GR, Pope JE. Novel treatment strategies in rheumatoid arthritis. The Lancet. 2017;389(10086):2338–2348.

Di Rocco et al., 2019 Di Rocco F, Rothenbuhler A, Cormier Daire V, et al. Craniosynostosis and metabolic bone disorder A review. Neurochirurgie. 2019;65(5):258–263.

Grabowski, 2009 Grabowski P. Physiology of bone. Endocrine development. 2009;16:32–48.

Horwitz et al., 1999 Horwitz EM, Prockop DJ, Fitzpatrick LA, et al. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nature Medicine. 1999;5(3):309–313.

Lu et al., 2019 Lu L, Dai C, Zhang Z, et al. Treatment of knee osteoarthritis with intra-articular injection of autologous adipose-derived mesenchymal progenitor cells: a prospective, randomized, double-blind, active-controlled, phase IIb clinical trial. Stem Cell Research & Therapy. 2019;10(1):143.

Marcacci et al., 2007 Marcacci M, Kon E, Moukhachev V, et al. Stem cells associated with macroporous bioceramics for long bone repair: 6- to 7-year outcome of a pilot clinical study. Tissue Engineering. 2007;13(5):947–955.

Quarto et al., 2001 Quarto R, Mastrogiacomo M, Cancedda R, et al. Repair of large bone defects with the use of autologous bone marrow stromal cells. The New England Journal of Medicine. 2001;344(5):385–386.

Sarzi-Puttini et al., 2005 Sarzi-Puttini P, Cimmino MA, Scarpa R, et al. Osteoarthritis: An overview of the disease and its treatment strategies. Seminars in Arthritis and Rheumatism. 2005;35(1):1–10 Supplement 1.

Sterneckert et al., 2014 Sterneckert JL, Reinhardt P, Schöler HR. Investigating human disease using stem cell models. Nature Reviews Genetics. 2014;15(9):625–639.

Tseng et al., 2008 Tseng SS, Lee MA, Reddi AH. Nonunions and the potential of stem cells in fracture-healing. The Journal of Bone and Joint Surgery. 2008;90(Suppl 1):92–98 . American volume.

Tu et al., 2018 Tu KN, Lie JD, Wan CKV, et al. Osteoporosis: a review of treatment options. P & T. 2018;43(2):92–104.

Undale et al., 2009 Undale AH, Westendorf JJ, Yaszemski MJ, Khosla S. Mesenchymal stem cells for bone repair and metabolic bone diseases. Mayo Clinic Proceedings.