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Comparative Analysis of the Therapeutic Effects of Fresh and Cryopreserved Human Umbilical Cord Derived Mesenchymal Stem Cells in the Treatment of Psoriasis

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Abstract

Psoriasis, an inflammatory autoimmune skin disease, is characterized by scaly white or erythematous plaques, which severely influence patients’ quality of life and social activities. Mesenchymal stem cells derived from the human umbilical cord (UCMSCs) represent a promising therapeutic approach for psoriasis because of its unique superiority in ethical agreeableness, abundant source, high proliferation capacity, and immunosuppression. Although cryopreservation provided multiple benefits to the cell therapy, it also greatly compromised clinical benefits of MSCs due to impaired cell functions. The current study aims to evaluate the therapeutic efficacy of cryopreserved UCMSCs in a mouse model of psoriasis as well as in patients with psoriasis. Our results showed that cryopreserved and fresh UCMSCs have comparable effects on the suppression of psoriasis-like symptoms such as thickening, erythema, and scaling, and serum IL-17 A secretion in mice model of psoriasis. Moreover, psoriatic patients injected with cryopreserved UCMSCs had a significant improvement in the Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA), and Patient Global Assessments (PtGAs) scores compared to baseline values. Mechanically, cryopreserved UCMSCs markedly inhibit the proliferation of PHA-activated PBMCs, type 1 T helper (Th1) and type 17 T helper (Th17) cell differentiation and secretion of inflammatory cytokines including IFN-γ, TNF-a and IL-17 A in PBMCs stimulated by anti-CD3/CD28 beads. Taken together, these data indicated that cryopreserved UCMSCs exhibited great beneficial effect on psoriasis. Thus, cryopreserved UCMSCs can be systemically administered as ‘‘off-the-shelf’’ cell product for psoriasis therapy. Trial Registration ChiCTR1800019509. Registered on November 15, 2018—Retrospectively registered, http://www.chictr.org.cn/.

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Data Availability

All data are available in the main manuscript or the supplemental information or provided upon availability and reasonable request.

Abbreviations

UCMSCs :

Umbilical cord-derived mesenchymal stem cells

IMQ :

Imiquimod

PHA :

Phytohemagglutinin

PASI :

Psoriasis Area Severity Index

H&E :

Hematoxylin and eosin

PGA :

Physician Global Assessment

PtGAs :

Patient Global Assessments

PBMC :

Peripheral blood mononuclear cell

Th1 :

Type 1 T helper

Th17 :

Type 17 T helper

UC :

Umbilical cord

UCMSCs (FL) :

Low dose of fresh UCMSCs

UCMSCs (FH) :

High dose of fresh UCMSCs

UCMSCs (CL) :

Low dose of cryopreserved UCMSCs

UCMSCs (CH) :

High dose of cryopreserved UCMSCs

SEM :

Standard error of the mean

hBMMSCs :

Human bone marrow derived MSCs

M :

Million

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Acknowledgements

The authors thank all of the MSC donors and the patients for their willingness to participate in this study. The authors also appreciate Yu Zhang, Chenxi Ge, Ziying Lin, Zhiqian Zhou, and Ke Liu at the Sinoneural Cell Engineering Group Holdings Co., Ltd. for their help with preparation of MSCs.

Funding

This work was sponsored by grants from National Natural Science Foundation of China (No. 81872522, 82073429, 82273510, 82203908), Innovation Program of Shanghai Municipal Education Commission (No.2019-01-07-00-07-E00046), Clinical Research Plan of SHDC (No. SHDC2020CR1014B, SHDC2020CR6022, SHDC12018X06) and Program of Shanghai Academic Research Leader (No. 20XD1403300).

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  1. Zhifeng Wang and Yifan Hu contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, China

    Zhifeng Wang, Yifan Hu, Youdong Chen & Yuling Shi

  2. Sinoneural Cell Engineering Group Holdings Co., Ltd, No. 1188, Lianhang Road, Shanghai, 201100, China

    Zhifeng Wang, Xiaoyu Wang, Danfeng Wu, Houli Ji, Cuicui Yu, Jingmeng Fang, Chunrong Pan, Lianjian Wang, Shouxin Wang, Yinhong Guo, Yi Lu, Di Wu, Fangfang Ren & Hao Zhu

  3. Institute of Psoriasis, Tongji University School of Medicine, Shanghai, 200443, China

    Yifan Hu, Youdong Chen & Yuling Shi

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Contributions

The study was designed by Z.W., D.F.W., H.J., H.Z., and Y.S.; The experiments were carried out by Z.W., Y.H., X.W., Y.C., C.Y., J.F., C.P., L.W., Y.G., Y.L., D.W., and F.R.; Z.W., X.W., C.Y., J.F., and S.W. wrote the paper; all authors analyzed the data; H.Z., and Y.S. supervised the project. All authors approved the final submitted version.

Corresponding authors

Correspondence to Zhifeng Wang, Hao Zhu or Yuling Shi.

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Ethics Approval and Consent to Participate

The number of animals used in the research as well as experimental procedures had been reviewed and approved by the Institutional Animal Care and Use Committee (IACUC No. ACU20-1719). Mouse care and experiments were performed following the National Institutes of Health Guide for the Care and Use of Laboratory Animals. The clinical study was approved by the Stem Cell Research Ethics Committee of Shanghai Tenth People’s Hospital of Tongji University, China (approval No. SC-2020-01).

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Consent for publication was obtained from every participant.

Competing Interests

The authors declare no competing interests. The authors from Sinoneural Cell Engineering Group Holdings Co., Ltd. helped in the preparation of the MSCs.

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Wang, Z., Hu, Y., Wang, X. et al. Comparative Analysis of the Therapeutic Effects of Fresh and Cryopreserved Human Umbilical Cord Derived Mesenchymal Stem Cells in the Treatment of Psoriasis. Stem Cell Rev and Rep 19, 1922–1936 (2023). https://doi.org/10.1007/s12015-023-10556-8

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