Abstract
Conventional treatments of osteoarthritis have failed to re-build functional articular cartilage. Tissue engineering clinical treatments for osteoarthritis, including autologous chondrocyte implantation, provides an alternative approach by injecting a cell suspension to fill lesions within the cartilage in osteoarthritic knees. The success of chondrocyte implantation relies on the availability of chondrogenic cell lines, and their resilience to high mechanical loading. We hypothesize we can reduce the numbers of human articular chondrocytes necessary for a treatment by supplementing cultures with human adipose-derived stem cells, in which stem cells will have protective and stimulatory effects on mixed cultures when exposed to high mechanical loads, and in which coculture will enhance production of requisite extracellular matrix proteins over those produced by stretched chondrocytes alone. In this work, adipose-derived stem cells and articular chondrocytes were cultured separately or cocultivated at ratios of 3:1, 1:1, and 1:3 in static plates or under excessive cyclic tensile strain of 10% and results were compared to culturing of both cell types alone with and without cyclic strain. Results indicate 75% of chondrocytes in engineered articular cartilage can be replaced with stem cells with enhanced collagen over all culture conditions and glycosaminoglycan content over stretched cultures of chondrocytes. This can be done without observing adverse effects on cell viability. Collagen and glycosaminoglycan secretion, when compared to chondrocyte alone under 10% strain, was enhanced 6.1- and 2-fold, respectively, by chondrocytes cocultivated with stem cells at a ratio of 1:3.
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Abbreviations
- AC:
-
articular cartilage
- ACAN:
-
aggrecan
- ACh:
-
articular chondrocytes
- ASC:
-
adipose-derived stem cells
- ACI:
-
autologous chondrocyte implantation
- ACTE:
-
articular cartilage tissue engineering
- ADAMTS-4:
-
a disintegrin and metalloproteinase with thrombospondin motif-4
- ADAMTS-4:
-
a disintegrin and metalloproteinase with thrombospondin motif-5
- BMSCs, bone marrow derived stem cells; BW:
-
body weight
- Col:
-
collagen
- COL2A1:
-
collagen type II alpha-1
- CTS:
-
cyclic tensile strain
- ECM:
-
extracellular matrix
- GAG:
-
glycosaminoglycan
- hAChs:
-
human articular chondrocytes
- hASCs:
-
human adipose-derived stem cells
- HDAC4:
-
histone deacetylase-4
- IL1-β:
-
interleukin1-beta
- IL-6:
-
interleukin-6
- I-κB:
-
inhibitor of nuclear factor kappa B
- MACI:
-
matrix-assisted chondrocyte implantation
- MMP-1:
-
matrix metalloproteinase-1
- MMP-13:
-
matrix metalloproteinase-13
- NF-κB:
-
nuclear factor kappa B
- OA:
-
osteoarthritis
- RUNX-2:
-
runt-related transcription factor-2
- SOX9:
-
SRY-Box Transcription Factor-9
- STC-1:
-
stanniocalcin-1
- TGF-β:
-
transforming growth factor-beta
- TIMP:
-
tissue inhibitors of metalloproteinases
- TKA:
-
total knee arthroscopy
- TSP-2:
-
thrombospondin-2
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Acknowledgments
The authors acknowledge (1) consenting participants who donated their cartilage samples post TKA; (2) Trey Reppe for assistance in isolating human chondrocytes from tissues; and (3) Nanosurface Biomedical Inc. for the academic discount for the Cytostretcher lease.
Funding
This work was done under the support of NSF, No. 1606226, and an NIH T32 grant, No. GM008336-31, with the latter providing trainee support for co-authors Haneen A. Abusharkh and Alia H. Mallah.
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Abusharkh, H.A., Mallah, A.H., Amr, M.M. et al. Enhanced matrix production by cocultivated human stem cells and chondrocytes under concurrent mechanical strain. In Vitro Cell.Dev.Biol.-Animal 57, 631–640 (2021). https://doi.org/10.1007/s11626-021-00592-4
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DOI: https://doi.org/10.1007/s11626-021-00592-4