The paracrine effect of adipose-derived stem cells inhibits osteoarthritis progression.
BACKGROUND
This study aimed to determine whether intra-articularly injected adipose-derived stem cells (ADSCs) inhibited articular cartilage degeneration during osteoarthritis (OA) development in a rabbit anterior cruciate ligament transection (ACLT) model. The paracrine effects of ADSCs on chondrocytes were investigated using a co-culture system.


METHODS
ACLT was performed on both knee joints of 12 rabbits. ADSCs were isolated from the subcutaneous adipose tissue. ADSCs with hyaluronic acid were intra-articularly injected into the left knee, and hyaluronic acid was injected into the right knee. The knees were compared macroscopically, histologically, and immunohistochemically at 8 and 12 weeks. In addition, cell viability was determined using co-culture system of ADSCs and chondrocytes.


RESULTS
Macroscopically, osteoarthritis progression was milder in the ADSC-treated knees than in the control knees 8 weeks after ACLT. Histologically, control knees showed obvious erosions in both the medial and lateral condyles at 8 weeks, while cartilage was predominantly retained in the ADSC-treated knees. At 12 weeks, the ADSC-treated knees showed a slight suppression of cartilage degeneration, unlike the control knees. Immunohistochemically, MMP-13 expression was less in the ADSC-treated cartilage than in the control knees. The cell viability of chondrocytes co-cultured with ADSCs was higher than that of chondrocytes cultured alone. TNF-alpha-induced apoptotic stimulation was similar between the two groups.


CONCLUSIONS
Intra-articularly injected ADSCs inhibited cartilage degeneration progression by homing to the synovium and secreting a liquid factor having chondro-protective effects such as chondrocyte proliferation and cartilage matrix protection.
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-8641, Japan. kurokazu0108@yahoo.co.jp.
Kazunari
K
Kuroda
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-8641, Japan. tamonkabata@yahoo.co.jp.
Tamon
T
Kabata
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-8641, Japan. hayashikatsu830@aol.com.
Katsuhiro
K
Hayashi
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-8641, Japan. torumaed@gmail.com.
Toru
T
Maeda
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-8641, Japan. torumaed@gmail.com.
Yoshitomo
Y
Kajino
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-8641, Japan. shntr.iwai@gmail.com.
Shintaro
S
Iwai
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-8641, Japan. kkkkkenji76@yahoo.co.jp.
Kenji
K
Fujita
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-8641, Japan. kazuhiro63hasegawa@gmail.com.
Kazuhiro
K
Hasegawa
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-8641, Japan. daisuke_i_0909@yahoo.co.jp.
Daisuke
D
Inoue
Department of Physiology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. ns@med.kanazawa-u.ac.jp.
Naotoshi
N
Sugimoto
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1, Takara-machi, Kanazawa, 920-8641, Japan. tsuchi@med.kanazawa-u.ac.jp.
Hiroyuki
H
Tsuchiya
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism / Q000637:transplantation; D018920:Coculture Techniques; D018450:Disease Progression; D005260:Female; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D019899:Paracrine Communication / Q000502:physiology; D011817:Rabbits; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000378:metabolism