Abstract
Conventional microcarriers used for expansion of human mesenchymal stem cells (hMSCs) require detachment and separation of the cells from the carrier prior to use in clinical applications for regeneration of articular cartilage, and the carrier can cause undesirable phenotypic changes in the expanded cells. This work describes a novel approach to expand hMSCs on biomimetic carriers based on adult or fetal decellularized bovine articular cartilage that supports tissue regeneration without the need to detach the expanded cells from the carrier. In this approach, the fetal or adult bovine articular cartilage was minced, decellularized, freeze-dried, ground, and sieved to produce articular cartilage microgels (CMGs) in a specified size range. Next, the hMSCs were expanded on CMGs in a bioreactor in basal medium to generate hMSC-loaded CMG microgels (CMG-MSCs). Then, the CMG-MSCs were suspended in sodium alginate, injected in a mold, crosslinked with calcium chloride, and incubated in chondrogenic medium as an injectable cellular construct for regeneration of articular cartilage. The expression of chondrogenic markers and compressive moduli of the injectable CMG-MSCs/alginate hydrogels incubated in chondrogenic medium were higher compared to the hMSCs directly encapsulated in alginate hydrogels.
Highlights
The expression of chondrogenic markers and compressive moduli of the injectable cartilage microgels (CMGs)-MSCs/alginate hydrogels incubated in chondrogenic medium were higher compared to the human mesenchymal stem cells (hMSCs) directly encapsulated in alginate hydrogels
It has been shown that the bone marrow or synovium derived hMSCs delivered in a supportive matrix promote the expression of chondrogenic markers and produce a cartilage-like matrix in vitro and in vivo [3–6]
It is well-established that fetal articular cartilage has a higher capacity to regenerate the complex stratified structure of articular cartilage compared to the adult, which is attributed to the differences in extracellular matrix (ECM) composition between the adult and fetal articular cartilage [7,8]
Summary
The elderly population, those over the age of 60, experience joint pain due to cartilage degeneration which leads to long-term disability and lower quality of life [1]. A promising approach is intervention with cellular therapies using autologous “adult human mesenchymal stem cells”, hereafter referred to as hMSCs. It has been shown that the bone marrow or synovium derived hMSCs delivered in a supportive matrix promote the expression of chondrogenic markers and produce a cartilage-like matrix in vitro and in vivo [3–6]. It has been shown that the bone marrow or synovium derived hMSCs delivered in a supportive matrix promote the expression of chondrogenic markers and produce a cartilage-like matrix in vitro and in vivo [3–6] It is well-established that fetal articular cartilage has a higher capacity to regenerate the complex stratified structure of articular cartilage compared to the adult, which is attributed to the differences in extracellular matrix (ECM) composition between the adult and fetal articular cartilage [7,8]. Novel engineering approaches are needed to recreate the structure and ECM composition of fetal articular cartilage to regenerate the injured tissue with cell therapy
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