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Isolation of stem cell populations with trophic and immunoregulatory functions from human intestinal tissues: potential for cell therapy in inflammatory bowel disease
- Source :
- Cytotherapy. 11:1020-1031
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stromal cells (MSC) are currently under evaluation in phase III clinical trials for inflammatory bowel disease and other intestinal disease manifestations. The therapeutic efficacy of these treatments may derive from a combination of the differentiation, trophic and immunomodulatory abilities of the transplanted cells. We investigated intestinal tissues as sources of MSC: such cells may support tissue-specific functions and hold advantages for engraftment and contribution in the gastrointestinal environment.Intestinal specimens were collected, and the mucosa and submucosa mechanically separated and enzymatically digested. Mesenchymal stromal populations were isolated, expanded and characterized under conditions commonly used for MSC. The differentiation potential, trophic effect and immunomodulatory ability were investigated. Results We successfully isolated and extensively expanded populations showing the typical MSC profile: CD29+, CD44+, CD73+, CD105+ and CD166+, and CD14(-), CD34(-) and CD45(-). Intestinal mucosal (IM) MSC were also CD117+, while submucosal cultures (ISM MSC) showed CD34+ subsets. The cells differentiated toward osteogenic, adipogenic and angiogenic commitments. Intestinal-derived MSC were able to induce differentiation and organization of intestinal epithelial cells (Caco-2) in three-dimensional collagen cultures. Immunomodulatory activity was evidenced in co-cultures with normal heterologous phytohemagglutinin-stimulated peripheral blood mononuclear cells. Conclusions Multipotent MSC can be isolated from intestinal mucosal and submucosal tissues. IM MSC and ISM MSC are able to perform trophic and immunomodulatory functions. These findings could open a pathway for novel approaches to intestinal disease treatment.
- Subjects :
- Cancer Research
Stromal cell
trophic function
intestinal stem cell
Immunology
Cell Culture Techniques
Neovascularization, Physiologic
Adipose tissue
Clinical uses of mesenchymal stem cells
Cell Separation
Biology
Inflammatory bowel disease
NO
Cell Line
Immunomodulation
Cell therapy
inflammatory bowel disease
stem cells
Osteogenesis
Submucosa
cell therapy, immunomodulation, inflammatory bowel disease, intestinal stem cell, mesenchymal stromal cells, stem cells, trophic function
medicine
Humans
Immunology and Allergy
Cell Lineage
Intestinal Mucosa
Phytohemagglutinins
Genetics (clinical)
Cell Proliferation
Transplantation
Mesenchymal stem cell
Cell Differentiation
Epithelial Cells
Mesenchymal Stem Cells
Cell Biology
Inflammatory Bowel Diseases
medicine.disease
Intestines
medicine.anatomical_structure
Oncology
cell therapy
Stem cell
mesenchymal stromal cells
Biomarkers
Stem Cell Transplantation
Subjects
Details
- ISSN :
- 14653249
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Cytotherapy
- Accession number :
- edsair.doi.dedup.....ea92cb5e723548a4db5537b5f9ce470f