Efficacy of matrilin-3-primed adipose-derived mesenchymal stem cell spheroids in a rabbit model of disc degeneration
- PDF / 2,012,226 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 36 Downloads / 158 Views
(2020) 11:363
RESEARCH
Open Access
Efficacy of matrilin-3-primed adiposederived mesenchymal stem cell spheroids in a rabbit model of disc degeneration Manjunatha S. Muttigi1†, Byoung Ju Kim2†, Hemant Kumar3, Sunghyun Park2,4, Un Yong Choi5, Inbo Han5*, Hansoo Park1* and Soo-Hong Lee2*
Abstract Background: Chronic low back pain is a prevalent disability, often caused by intervertebral disc (IVD) degeneration. Mesenchymal stem cell (MSC) therapy could be a safe and feasible option for repairing the degenerated disc. However, for successful translation to the clinic, various challenges need to be overcome including unwanted adverse effects due to acidic pH, hypoxia, and limited nutrition. Matrilin-3 is an essential extracellular matrix (ECM) component during cartilage development and ossification and exerts chondrocyte protective effects. Methods: This study evaluated the effects of matrilin-3-primed adipose-derived MSCs (Ad-MSCs) on the repair of the degenerated disc in vitro and in vivo. We determined the optimal priming concentration and duration and developed an optimal protocol for Ad-MSC spheroid generation. Results: Priming with 10 ng/ml matrilin-3 for 5 days resulted in the highest mRNA expression of type 2 collagen and aggrecan in vitro. Furthermore, Ad-MSC spheroids with a density of 250 cells/microwell showed the increased secretion of favorable growth factors such as transforming growth factor beta (TGF-β1), TGF-β2, interleukin-10 (IL10), granulocyte colony-stimulating factor (G-CSF), and matrix metalloproteinase 1 (MMP1) and decreased secretion of hypertrophic ECM components. In addition, matrilin-3-primed Ad-MSC spheroid implantation was associated with optimal repair in a rabbit model. Conclusion: Our results suggest that priming MSCs with matrilin-3 and spheroid formation could be an effective strategy to overcome the challenges associated with the use of MSCs for the treatment of IVD degeneration. Keywords: Intervertebral disc, Degeneration, Mesenchymal stem cell, Matrilin-3, Priming, Spheroid, Engineered MSCs
* Correspondence: [email protected]; [email protected]; [email protected] † Manjunatha S. Muttigi and Byoung Ju Kim contributed equally to this work. 5 Department of Neurosurgery, School of Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 13496, South Korea 1 School of Integrative Engineering, Chung-Ang University, Seoul 06911, South Korea 2 Department of Medical Biotechnology, Dongguk University-Seoul, Seoul 04620, South Korea Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons
Data Loading...
