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Index
Remerciements ... 1
Citation ... 3
Composition of the thesis’ Assessment Panel ... 4
Abbreviations ... 6
Résumé de la thèse ... 10
Thesis summary ... 11
Index ... 12
1. Introduction ... 15
1.1. What are multipotent mesenchymal stromal cells? A short definition ... 15
1.2. Brief history ... 16
1.3. Stem cells ... 17
1.3.1. General information on stem cells: ... 17
1.3.2. Stem cell niches ... 18
1.3.3. Are MSC stem cells? ... 18
1.4. MSC sources... 19
1.4.1. Bone marrow (BM) ... 19
1.4.2. Adipose tissue (AT) ... 20
1.4.3. Alternative sources ... 20
1.5. MSC properties... 22
1.5.1. Hematopoiesis support ... 24
1.5.2. Multipotency potential... 26
1.5.3. Secretion and trophic support ... 26
1.5.4. Immunoregulation potential ... 27
1.5.5. Mobilization and homing ... 29
1.5.6. Extracellular vesicles ... 29
1.6. Clinical applications of MSC ... 31
1.6.1. Hematological pathologies and GVHD ... 34
1.6.2. Cardiovascular diseases ... 35
1.6.3. Bone and cartilage diseases ... 36
1.6.4. Autoimmune diseases ... 37
1.6.5. Neurodegenerative diseases and neurological disorders ... 38
1.6.6. Solid organ transplantation ... 42
1.6.7. Wound healing ... 43
1.6.8. Pulmonary clinical applications ... 44
1.7. Isolation methods ... 46
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1.7.2. Microrafts array ... 49
1.7.3. DEPArray™ Technology ... 51
1.7.4. FACS ... 51
1.7.5. Immunoselection ... 51
1.8. In situ phenotype or cell surface markers useful for MSC isolation ... 53
1.8.1. Stro-1 ... 53 1.8.2. CD105 and CD73 ... 54 1.8.3. CD90 ... 54 1.8.4. CD44 ... 54 1.8.5. MSCA-1 ... 55 1.8.6. CD200 ... 55 1.8.7. SUSD2 ... 55 1.8.8. CD271 ... 55 1.8.9. CD34 ... 56 1.8.10. CD106 ... 57 1.8.11. CD146 ... 58
2. Issues: heterogeneity and subpopulations of MSC ... 59
3. Aims of the work ... 62
4. Results/publications ... 63
4.1. Isolation of adipose-derived stromal cells without enzymatic treatment: expansion, phenotypical, and functional characterization. ... 63
4.1.1. Summary ... 63
4.1.2. Published article ... 64
4.2. Isolation and characterization of human mesenchymal stromal cells subpopulations: comparison of bone marrow and adipose tissue. ... 78
4.2.1. Summary ... 78
4.2.2. Published article ... 79
5. Discussion and conclusion ... 103
6. Future goals ... 110
7. Global perspectives ... 112
8. Reference List... 116
9 Annexes of the thesis ... 137
9.1. Addendum ... 137
9.1.1. Immunomodulation activities of ADSC ... 137
9.1.2. Comparison of collagenase and Liberase for the isolation of ADSC ... 138
9.2. Curriculum Vitae ... 139
