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Human dental pulp stem cells have comparable abilities to umbilical cord mesenchymal stem/stromal cells in regulating inflammation and ameliorating hepatic fibrosis

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Abstract

Hepatic fibrosis, also called cirrhosis, have wide prevalence worldwide for long yeas. Recently, many treatments for liver cirrhosis made marked progress, especially the umbilical cord-derived mesenchymal stromal cells (UCMSC) therapy. However, limited recourses and potential immune-related issues become the obstacles on UCMSC popularization in clinic. Therefore, we took dental pulp stem cells (DPSCs) into the consideration, since autologous DPSCs can be easily obtained without any ethnic or immune-related issues that heterogenous UCMSCs could encounter. We systematically compared the effects of both cell types and found that DPSCs had similar results to UCMSCs in regulating inflammation and reversing hepatic fibrosis. In our study, co-culturing T cells and PBMSCs showed that DPSCs have the ability to inhibit the proliferation of inflammatory cells and downregulate relevant inflammatory factors. In vitro and in vivo sterility tests confirmed the bio-safety of DPSCs. Moreover, the 1 year-aged mouse model demonstrated that DPSCs successfully reversed hepatic fibrosis. Overall, DPSCs demonstrated comparable effectiveness to UCMSCs in regulating inflammation and reversing hepatic fibrosis, particularly in the aged mouse model that represents middle-aged and elderly humans. Since autologous DPSCs avoid potential immune-related issues that heterogenous UCMSCs could encounter, they may be a better choice for stem cell-related therapies.

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Data availability

The materials and data used and/or analyzed in the present study are available from the corresponding author on reasonable request.

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Author notes

  1. Peixing Chen and Yanchun Lin contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, 515000, Guangdong, China

    Peixing Chen, Wenbo Lin & Kaitao Yao

  2. Department of Stem Cell Research Center, Guangdong Procapzoom Biosciences, Inc., 11 Guangpuzhong Rd., Guangzhou, 510000, Guangdong, China

    Yanchun Lin, Yun Li, Ting Fu, Yuanyue Liu, Tian Guan, Man Xin, Ling Ye, Peiluan Wang & Haoyu Zeng

Authors
  1. Peixing Chen
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Contributions

KY and HZ designed the study and supervised the research process. PC and WL collected the materials and samples. YL and YL performed the in vitro experiment of DPSC and UCMSC comparison. PC, WL, YL and TG performed the in vivo experiments. MX, LY and PW conducted the additional experiments and provided the supplementary data. PC drafted the manuscript. HZ and KY reviewed the manuscript and approved submission.

Corresponding authors

Correspondence to Haoyu Zeng or Kaitao Yao.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval and consent to publish

All the feeding and experiment of using animals were following the guideline for animal ethical and welfare, and approved by the animal ethics committee of Shantou University Medical College (No. SUMC2022). All the using specimens from patients were approved by The Second Affiliated Hospital of Shantou University Medical College, and the informed consent was obtained from each patient.

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Supplementary Information

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13577_2023_1004_MOESM1_ESM.tif

Supplementary file1 In this study, the relevant mRNA expression of DPSCs and USMSCs in trilineage differentiation was investigated. The mRNA expression levels of RUX2, BGLAP, PPARG, COL10, COL2, and SOX9 were measured using qRT-PCR and were subsequently normalized to the control groups of DPSCs and USMSCs. Statistical significance was determined by comparing the P-values obtained, with values less than 0.05 considered statistically different and denoted by "*". For P-values less than 0.01, the symbol "**" was used (TIF 689 KB)

13577_2023_1004_MOESM2_ESM.tif

Supplementary file2 H&E staining of mice liver tissues. The liver tissues from mice in the treatment group were fixed using paraformaldehyde, sliced, and stained with hematoxylin and eosin. Subsequently, images of the stained tissues were captured using a 10x microscope lens (TIF 32056 KB)

13577_2023_1004_MOESM3_ESM.tif

Supplementary file3 Immunohistochemistry staining and western blot analyses for the expression of α-SMA in mice liver tissues. The liver tissues were either fixed using paraformaldehyde or lysed with RIPA buffer containing a proteinase inhibitor. Subsequently, α-SMA protein expression was detected through immunohistochemistry staining and western blot development (TIF 48780 KB)

Supplementary file4 (DOCX 16 KB)

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Chen, P., Lin, Y., Lin, W. et al. Human dental pulp stem cells have comparable abilities to umbilical cord mesenchymal stem/stromal cells in regulating inflammation and ameliorating hepatic fibrosis. Human Cell 37, 204–213 (2024). https://doi.org/10.1007/s13577-023-01004-3

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  • DOI: https://doi.org/10.1007/s13577-023-01004-3

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