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Ultrasound-guided Intracardiac Injection of Human Mesenchymal Stem Cells to Increase Homing to the Intestine for Use in Murine Models of Experimental Inflammatory Bowel Diseases
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Adipose-Derived Stem Cells From Patients With Ulcerative Colitis Exhibit Impaired Immunosuppressive Function.

Xiaoyun Wu1,2,3, Yongxu Mu3, Jingyi Yao4

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Frontiers in Cell and Developmental Biology
|March 7, 2022
PubMed
Summary

Adipose-derived stem cells (ADSCs) from ulcerative colitis (UC) patients show reduced immune-modulating abilities compared to those from healthy donors. This defect suggests autologous ADSC therapy may be unsuitable for treating UC patients.

Keywords:
adipose stem cellsautoimmune diseaseautologous stem cell transplantationimmunosuppressionmesenchymal stem cells

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Area of Science:

  • Immunology
  • Stem Cell Biology
  • Gastroenterology

Background:

  • Adipose-derived stem cells (ADSCs) are explored for ulcerative colitis (UC) treatment due to their immune-modulating properties.
  • Concerns exist regarding potential defects in ADSCs from patients with inflammatory or autoimmune diseases, impacting their therapeutic efficacy.

Purpose of the Study:

  • To compare the functional and immunosuppressive characteristics of ADSCs from healthy donors (H-ADSCs) and UC patients (P-ADSCs).
  • To evaluate the therapeutic potential of P-ADSCs in mouse models of colitis.

Main Methods:

  • Comparative analysis of ADSC morphology, proliferation, differentiation, and immunomodulatory functions (cytokine secretion, immune cell suppression).
  • Assessment of P-ADSC immunosuppressive capacity via peripheral blood mononuclear cell proliferation assays and cytokine analysis.
  • In vivo efficacy testing of P-ADSCs versus H-ADSCs in acute and chronic colitis mouse models.

Main Results:

  • P-ADSCs demonstrated reduced proliferative and differentiation capacities compared to H-ADSCs.
  • P-ADSCs exhibited significantly diminished immunosuppressive functions, including lower inhibition of T-cell proliferation and reduced secretion of key immunomodulatory factors like prostaglandin E2.
  • In colitis models, P-ADSCs showed weaker therapeutic effects than H-ADSCs, evidenced by increased disease activity and poorer histological outcomes.

Conclusions:

  • ADSCs from UC patients possess inherent functional defects, particularly in immunosuppression, linked to donor metabolic characteristics.
  • The findings challenge the suitability of autologous ADSC transplantation for UC treatment, highlighting potential limitations in immune modulation.