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TR1 cells, mesenchymal stem cells and uses thereof

A kind of stem cell and cell technology, applied in the field of Tr1 cells and mesenchymal stem cells, can solve the problem of low degree of proliferation

Inactive Publication Date: 2010-09-15
TXCELL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These Tr1 cells produce IL-10, IL-5, and IFN-γ, with or without TGF-β, but with little or no IL-2 or IL-4, and in polyclonal TCR-mediated activation Post-proliferation is very low

Method used

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  • TR1 cells, mesenchymal stem cells and uses thereof
  • TR1 cells, mesenchymal stem cells and uses thereof
  • TR1 cells, mesenchymal stem cells and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0151] Preparation of MSCs

[0152] Mesenchymal stem cells were obtained from the stromal-vascular fraction of adipose tissue of Balb / c mice. Adipose tissue was digested with 0.1% collagenase for 30 minutes and filtered through a 70μ mesh. Adherent cells were cultured in RPMI medium containing 10% FCS and 10% horse serum supplemented with glutamine and penicillin and streptomycin. Cells were frequently monitored for their ability to differentiate into adipocyte and osteoblast lineages.

[0153] Preparation of Tr1 cells

[0154] Ovalbumin-specific Tr1 cells were derived from DO11-10 ovalbumin-specific TCR transgenic mice activated with ovalbumin peptide 323-339 and IL-10 in the presence of irradiated isogenic antigen-presenting cells Differentiate from naive CD4+ T lymphocytes. Cells were then cloned by limiting dilution to obtain a monoclonal population of ovalbumin-specific Trl cells. Cells used in experiments 1 and 2 were obtained from cultures of the Trl clone.

...

Embodiment 2

[0162] BALB / c mice were treated with Dextran Sodium Sulfate (DSS, 5% drinking water in water) to induce acute colitis. One group of mice was not treated, or was treated with or without MSCs (0.5×10 6 / mouse) of 10 6 Ovalbumin-specific Tr1 cells were treated intravenously. After 7 days, mice were evaluated for clinical signs based on the following scores:

[0163] 0 - no clinical signs

[0164] 1- Weight Loss

[0165] 2- Weight loss + mild diarrhea

[0166] 3- Weight loss + severe diarrhea

[0167] 4- Weight loss + severe diarrhea + bloody stool

[0168] The results show that co-administration of MSCs can improve the efficacy of Tr1 cell therapy in this model of colitis ( figure 2 ).

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Abstract

The present invention relates to compositions comprising Tr1 cells and mesenchymal stem cells and methods for treating an autoimmune disease, an allergic disease or an inflammatory disease.

Description

technical field [0001] The present invention relates to Tr1 cells and mesenchymal stem cells. More specifically, the present invention relates to the use of Tr1 cells and mesenchymal stem cells for the treatment of excessive, dysfunctional or uncontrolled self or non-self T cell mediated responses, such as autoimmune diseases or inflammatory disease. Background technique [0002] The function of the immune system is to eliminate foreign cells that may contain pathogens, while maintaining anergy, or tolerance, to self-antigens. Tolerance manifests itself as exhaustion of autoreactive T cells or anergy, the latter characterized by viable but low reactivity of T cells. In several circumstances, however, the immune system can attack components of itself, causing autoimmune disease. Autoimmune diseases are thought to be caused by an abnormal immune response to self-antigens due to altered immunogenicity of the self-antigens or exposure to cross-reactive mimic antigens. [000...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/06C12N5/08A61K39/00C12N5/0775C12N5/0783
CPCC12N5/0667C12N5/0636C12N2501/23A61P1/02A61P1/04A61P1/16A61P11/02A61P11/06A61P19/02A61P25/00A61P29/00A61P35/00A61P37/02A61P37/06A61P37/08A61P9/00A61P9/10A61P3/10A61K39/4621A61K39/4644A61K2239/31A61K2239/38A61K39/4611A61K39/46433
Inventor 阿尔诺·福萨特纳萨莉·贝尔蒙特
Owner TXCELL