Stem cell-based therapies for osteoarthritis

Abstract

Purpose of review Regenerative medicine offers the exciting potential of developing alternatives to total joint replacement for treating osteoarthritis (OA). In this article, we highlight recent work that addresses key challenges of stem cell-based therapies for OA and provide examples of innovative ways in which stem cells can aid in the treatment of OA. Recent findings Significant progress has been made in understanding the challenges to successful stem cell therapy, such as the effects of age or disease on stem cell properties, altered stem cell function due to an inflammatory joint environment, and phenotypic instability in vivo. Novel scaffold designs have been shown to enhance the mechanical properties of tissue-engineered cartilage and have also improved the integration of newly formed tissue within the joint. Emerging strategies such as injecting stem cells directly into the joint, manipulating endogenous stem cells to enhance regenerative capacity, and utilizing stem cells for drug discovery have expanded the potential uses of stem cells in treating OA. Summary A number of recent studies have greatly advanced the development and pre-clinical evaluation of potential stem cell-based treatments for OA through novel approaches focused on cell therapy, tissue engineering, and drug discovery.

Infrapatellar Fat Pad-Derived Stem Cells Maintain Their Chondrogenic Capacity in Disease and Can be Used to Engineer Cartilaginous Grafts of Clinically Relevant Dimensions

“…Of course, there are still a number of outstanding questions that need to be addressed (in addition to the other challenges that have been highlighted above) before this can become a clinical reality. Many of these relate to any stem cell-based therapy proposed for the treatment of osteoarthritis, 5 but outstanding questions specific to the proposed approach include concerns related to the in vivo phenotypic stability of grafts engineered using FPSCs 78 and how such tissues will adopt and respond to joint specific environmental cues following implantation into loadbearing defects. Notwithstanding these concerns, the results of this study motivate the continued investigation of such tissue engineering strategies, as these grafts may ultimately be used to resurface entire joint surfaces and hopefully delay or prevent the need for total joint replacement prostheses.…”

“…6 While such an approach provides a promising putative treatment option for repairing large cartilaginous defects, it remains uncertain if chondrocytes isolated from articular cartilage represent a viable cell source for the osteoarthritic patient population due to age-and disease-related declines in their chondrogenic potential. 7,8 This had led to increased interest in the use of stem cells for cartilage tissue engineering applications, 5 from embryonic stem cells 9 to adult mesenchymal stem cells or multipotent stromal cells (MSCs) isolated from tissues, such as bone marrow (BM), [10][11][12] adipose tissue, [13][14][15][16] synovial tissue, 17,18 or infrapatellar (Hoffa's) fat pad (IFP), 19,20 to induced pluripotent stem cells. 21 From all these options, autologous adult MSCs may represent the least challenging cell source from a regulatory perspective.…”

“…In recent years, there has been increased interest in the use of stem cells as part of a new treatment paradigm for osteoarthritis. 5 One putative route to joint regeneration would be to replace the entire articular surface of a diseased joint with a tissue-engineered cartilaginous or osteochondral graft. Realizing such a transformative treatment option for osteoarthritis requires a number of biological and technical challenges to be overcome, in particular, the identification of a cell source suitable for use in the osteoarthritic (OA) patient population, as well as the development of novel approaches for engineering functional grafts of a geometric scale necessary to resurface an entire joint.…”

Near infrared spectroscopic evaluation of water in hyaline cartilage

“…In addition, the probability of success of novel therapies for OA likely depend on early diagnosis and thus earlier therapeutic intervention. Several disease modifying therapies are proposed in the literature to treat OA, such as non-drug therapies (exercise, weight loss), drug therapies (intra-articular corticosteroid injections, non-steroidal anti-inflammatory drugs (NSAIDs) 54 , cell based therapies (stem cells injections) 20 and surgical procedures (debridement, microfracture 25; 29 , autologous chondrocyte implantation (ACI) 7 . Near infrared fiber optic probe analysis could be a useful tool for assessment of therapeutic efficacy, as well as during debridement procedures to aid in determination of the margins of healthy versus degraded tissue areas.…”

Cell Therapy for Osteoarthritis

“…The limitation of ACI for the OA treatment demanded the emergence of another cell source. Stem cells proved to be a promising candidate for the cartilage regeneration [12]. Stem cells are the undifferentiated cells that are capable of differentiating into specialized cells such as osteocytes, chondrocytes, adipocytes etc.…”