Frequent injections of high-dose human umbilical cord mesenchymal stem cells slightly aggravate arthritis and skeletal muscle cachexia in collagen-induced arthritic mice

Lemei An; Tianshu Chu; Liujun Wang; Songtao An; Yalong Li; Hongbo Hao; Zhuoli Zhang; Han Yue

doi:10.3892/etm.2021.10707

Frequent injections of high-dose human umbilical cord mesenchymal stem cells slightly aggravate arthritis and skeletal muscle cachexia in collagen-induced arthritic mice

Exp Ther Med. 2021 Nov;22(5):1272. doi: 10.3892/etm.2021.10707. Epub 2021 Sep 7.

Authors

Lemei An¹, Tianshu Chu¹, Liujun Wang¹, Songtao An², Yalong Li³, Hongbo Hao⁴, Zhuoli Zhang⁵, Han Yue³

Affiliations

¹ Department of Rheumatology and Clinical Immunology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R. China.
² Department of Cardiology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R. China.
³ Henan Key Laboratory of Stem Cell Differentiation and Modification, Stem Cell Research Center, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R. China.
⁴ Neuroscience Initiative, Advanced Science Research Center at the Graduate Center, City University of New York, New York, NY 10031, USA.
⁵ Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing 100034, P.R. China.

Abstract

A single injection of low-dose human umbilical cord-derived mesenchymal stem cells (UC-MSCs) has been previously demonstrated to relieve synovitis and bone erosion in animal models of arthritis, but whether frequent injections of high-dose UC-MSCs relieve arthritis and inhibit loss of muscle mass has remained elusive. In the present study, DBA/1 mice were randomly divided into three groups: Normal (wild-type mice; n=11), collagen-induced arthritis (CIA; n=12) and CIA treated with UC-MSCs (n=11; 5x10⁶ UC-MSCs per week for 3 weeks). Arthritis and skeletal muscle cachexia were evaluated until the end of the experiment on day 84. It was indicated that both the CIA and UC-MSC groups had lower body weights compared with the normal mice. Clinical arthritis scores, hind ankle diameters, synovitis and bone erosion progressively increased and were similar between the CIA and UC-MSC groups. Although there was no difference in food intake among the three groups, the normalized food intake of normal group was significantly higher than CIA group and UC-MSC group from day 42 onwards; there was no significance on day 77 but this could be neglected. Furthermore, gastrocnemius muscle weight in the UC-MSC group was significantly reduced compared with that in the CIA and normal groups. The UC-MSC group had higher levels of proinflammatory cytokines, such as TNF-α, IL-6 and IL-1β than those in the CIA group. However, the other cytokines assessed and the fibrosis indices in the CIA and UC-MSC groups were not different from those in the control group and there was no inflammatory cell infiltration. Thus, frequent injections of high-dose UC-MSCs slightly aggravated synovitis and muscle cachexia in the murine CIA model and should therefore be avoided in the treatment of arthritis.

Keywords: fibrosis; human umbilical cord mesenchymal stem cells; inflammation; muscle cachexia; rheumatoid arthritis.

Grants and funding

Funding: The present study was supported by the Science and Technology Department of Henan Province (grant no. 212102310200) and the National Natural Science Foundation of China (grant no. 81970312).