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Abstract
The evolution of articular cartilage repair procedures has resulted in a variety of cell-based therapies that use both autologous and allogeneic mesenchymal stromal cells (MSCs). As these cells are increasingly available and show promising results both in vitro and in vivo, cell-based strategies, which aim to improve ease of use and cost-effectiveness, are progressively explored. The use of MSCs in cartilage repair makes it possible to develop single-stage cell-based therapies. However, true single-stage procedures rely on one intervention, which will limit cell sources to fraction concentrates containing autologous MSCs or culture-expanded allogeneic MSCs. So far, it seems both autologous and allogeneic cells can safely be applied, but clinical studies are still ongoing and little information on clinical outcome is available. Further development of cell-based therapies may lead to clinical-grade, standardized, off-the-shelf products with easy handling for orthopedic surgeons. Although as of yet no preclinical or clinical studies are ongoing which explore the use of induced pluripotent stem cells for cartilage repair, a good manufacturing practice-grade induced pluripotent stem cell line might become the basis for such a product in the future, providing that cell fate can be controlled. The use of stem cells in clinical trials brings along new ethical issues, such as proper controls and selecting primary outcome measures. More clinical trials are needed to estimate detailed risk-benefit ratios and trials must be carefully designed to minimize risks and burdens for patients while choosing outcome measures that allow for adequate comparison with results from similar trials. In this review, we discuss the different aspects of new stem cell-based treatments, including safety and ethical issues, as well as provide an overview of current clinical trials exploring these approaches and future perspectives.
Highlights
Cartilage defects in the weight-bearing joint are a severe limitation to the patient and pose a significant burden to society
The fate of Mesenchymal stromal cell (MSC) in vivo remains unknown: will they survive or disappear in the long-term? Will they all differentiate into chondrocytes or will some remain as MSCs? Current studies are not conclusive on these questions; some have suggested MSCs differentiate and survive in vivo up to 6 months, while others suggest MSCs have a chondroinductive role - that is, stimulate cartilage regeneration through trophic factors while slowly disappearing from the culture [4]
This is supported by the findings in the level IV and V evidence studies that used Bone marrow-derived mesenchymal stromal cell (BMMSC) or Bone marrow concentrate (BMC) for cartilage repair; all have reported clinical improvement with a follow-up period ranging from 1 year to 5 years [25,27,28,29,30,31,32,35,36,38,39,40]
Summary
Cartilage defects in the weight-bearing joint are a severe limitation to the patient and pose a significant burden to society. Isolated BMMSCs and bone marrow concentrates (BMCs) are most commonly used for treatment of cartilage defects in a clinical trial setting (Table 1). One study compared the use of two MSC-based treatments for cartilage repair [40].
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