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Combined Mesenchymal Stem Cells and Cartilage Acellular Matrix Injection Therapy for Osteoarthritis in Goats

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Human umbilical cord blood-derived MSCs (hUCB-MSCs) have been studied in osteoarthritis (OA) and cartilage regeneration. Our previous study demonstrated that hUCB-MSCs combined with cartilage acellular matrix injection (CAM Inj.) represent potential therapeutic agents for structural improvement and anti-inflammatory effects in a rabbit model of OA.

Methods:

Based on a previous study, this study has evaluated the safety and efficacy of hUCB-MSCs combined with CAM Inj. in an anterior cruciate ligament transection (ACLT) with medial meniscectomy (MMx) in a goat model. In this study, 27 goats were divided into 5 groups: normal (n = 3), OA (n = 6), OA + CAM Inj. (n = 6), OA + hUCB-MSCs (n = 6), and OA + hUCB-MSCs + CAM Inj. (n = 6). Lameness and radiographic parameters were assessed 6 months after administration, and macroscopic and histological evaluations of the goat articular cartilage were performed 6 months after intervention.

Results:

The results showed significant improvement in lameness score only in the OA + hUCB-MSCs group at 5 months after treatment (*p < 0.05), whereas the K&L score showed significant improvement only in the OA + hUCB-MSCs + CAM Inj. group 6 months after intervention (*p < 0.05). In addition, the gross findings showed significance in OA + CAM Inj. and OA + hUCB-MSCs + CAM Inj. groups 6 months after treatment (*p < 0.05 and **p < 0.01).

Conclusion:

In conclusion, treatment with a combination of hUCB-MSCs and CAM Inj. reduced OA symptoms and induced effective cartilage tissue repair in a goat model. We suggest the combination of hUCB-MSCs and CAM Inj. as an alternative therapy for OA.

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Acknowledgements

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: H I20C0233).

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Authors and Affiliations

  1. Stem Cell and Regenerative Bioengineering Institute, Global R&D Center, Kangstem Biotech Co. Ltd., Ace Highend Tower 8, 84, Gasan digital 1-ro, Geumcheon-gu, Seoul, 08590, Republic of Korea

    Mijin Kim, Jongchan Ahn, Jusik Lee, Seongsoo Song, Seunghee Lee, Seunghee Lee & Kyung-Sun Kang

  2. Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea

    Kyung-Sun Kang

  3. Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea

    Kyung-Sun Kang

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  1. Mijin Kim
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Correspondence to Seunghee Lee or Kyung-Sun Kang.

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Animal experiments were approved by the Experimental Animal Ethics Committee of KPC Co., Ltd. (approval no.: P18042).

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Supplementary Figure S1. Schematic illustration of the experimental procedure (Test 2). (TIF 34631 kb)

13770_2021_407_MOESM2_ESM.tif

Supplementary Figure S2. Clinical analysis of OA symptoms in a goat model (Test 2). A: Main lameness score over the study period. B: Representative radiological images of knee joints of experimental goats at 12 months. C: Radiological score according to the K&L scale at initial, 3, 6, 9 and 12 months. D: Representative gross images of the femoral condyle. The black circle indicates the defects or repaired lesion. E: Comparison of the gross finding scores of the lesion in the affected articular cartilage. F: Microscopic lesions of the articular cartilage in the affected knees of all experimental groups (Scale bars = 1 mm). G: Comparison of the modified OARSI histopathologic scores in the affected articular cartilage. Results represent means ± SEM, *p < 0.05. OA: osteoarthritis, K&L: Kellgren & Lawrence, COL2: Type 2 collagen. (TIF 19941 kb)

13770_2021_407_MOESM3_ESM.tif

Supplementary Figure S3. Histological evaluation of the synthesis of cartilaginous ECM on hUCB-MSCs pellet. A: Protein expression levels of COL2 in CAM Inj.. B: COL2 staining of hUCB-MSCs pellets (Scale bars = 200 μm). ECM; extracellular matrix, hUCB-MSCs: Human Umbilical cord blood-mesenchymal stem cell, COL2: Type 2 collagen. (TIF 27699 kb)

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Kim, M., Ahn, J., Lee, J. et al. Combined Mesenchymal Stem Cells and Cartilage Acellular Matrix Injection Therapy for Osteoarthritis in Goats. Tissue Eng Regen Med 19, 177–187 (2022). https://doi.org/10.1007/s13770-021-00407-3

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