Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

Abstract

Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

Comparison of adipose stem cells sources from various locations of rat body for their application for seeding on polymer scaffolds

“…This study highlights the current types of scaffolds, their uses, advantages, and limitations in stem cell tissue engineering applications and in regenerative medicine. It also highlights 3 D scaffolds, which are the most suitable scaffolds for delivering cells in vivo; moreover, for developing engineered tissues, different mechanical property/ porosity relationships and emerging applications in soft tissue engineering have been proposed [58,59] Assessment of various variants of culture media enriched with osteoinductive agents is a valuable comparative analysis potentially applicable for further optimization of pre-clinical strategies based on growth factors and biomaterials in skeletal engineering. BMP2 and FGF2 significantly increase ASC cell mineralization and induce osteogenesis.…”

Fiber Reinforced Cartilage ECM Functionalized Bioinks for Functional Cartilage Tissue Engineering

“…Over the past 25 years, numerous tissue engineering strategies have emerged for regenerating AC . Mesenchymal stem cells (MSCs) are also widely being used as an alternative to chondrocytes for cartilage tissue engineering . To successfully engineer cartilage‐like tissue using MSCs, it is critical to develop biomaterials that i) provide a microenvironment conducive to a stable chondrogenic phenotype, ii) provide mechanical integrity, and iii) possess the capacity to deliver growth factors and other regulatory biomolecules.…”

Therapeutic Potential of Dental Pulp Stem Cells and Leukocyte- and Platelet-Rich Fibrin for Osteoarthritis

“…The suggested mechanisms via which MSCs mediate cartilage repair and aid in OA include replacement of damaged cartilage tissue and paracrine-mediated effects such as proliferation of endogenous cells and immunomodulation [2].…”

“…Articular cartilage (AC) plays key roles in the function of diarthrodial (synovial) joints [1,2]. Cartilage injuries are very common, predominantly in young and active athletes, and particularly in the knee joint [3][4][5].…”

“…Cartilage injuries are very common, predominantly in young and active athletes, and particularly in the knee joint [3][4][5]. They are often considered as risk factors for the development of osteoarthritis (OA) in later life, a degenerative and inflammatory condition of the synovial joint with irreversible cartilage loss [2]. OA results in disability, particularly in elderly people and is associated with a large socio-economic burden [6,7].…”