Principle of MSC (Mesenchymal Stem Cell)
Therapeutic Efficacy of MSC Transplantation for Diabetic Cardiomyopathy
(a) MSCs upregulate MMP-2 activation and suppress MMP-9 activation, thereby attenuating adverse cardiac remodeling. (b) MSCs secrete VEGF, IGF-1, AM, and HGF, effectively stimulating myogenesis and angiogenesis within the damaged myocardium. (c) Through targeted differentiation into cardiomyocytes and vascular endothelial cells, MSCs significantly enhance myocardial perfusion and drive myocardial regeneration.
Abbreviation
AM (Adrenomedullin), HGF (Hepatocyte Growth Factor), IGF-1 (Insulin-like Growth Factor-1), MMP (Matrix Metalloproteinase), MSC (Mesenchymal Stem Cells), VEGF (Vascular Endothelial Growth Factor)
Therapeutic Efficacy of MSC Therapy for Diabetic Polyneuropathy
Four weeks post-intramuscular injection, MSCs engraft within the interstitial spaces of muscle fibers. By secretorily upregulating bFGF and VEGF production, they effectively induce angiogenesis and foster an environment that supports neurogenesis, ultimately driving the therapeutic alleviation of diabetic polyneuropathy.
Abbreviation
bFGF (basic fibroblast growth factor), MSC (mesenchymal stem cells), VEGF (vascular endothelial growth factor)
Intravenous (IV) Infusion and Systemic Administration of MSCs
Systemic administration of mesenchymal stem cells (MSCs) can elicit distal (endocrine) or localized (paracrine) therapeutic outcomes, driven by robust cell-mediated mechanisms.
1) Vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), monocyte chemoattractant protein 1 (MCP1), basic fibroblast growth factor (bFGF), interleukin 6 (IL-6)
2) Stem cell proliferation and differentiation: Stem cell factor (SCF), leukemia inhibitory factor (LIF), macrophage colony-stimulating factor (MCSF), stroma cell-derived factor 1 (SDF1), angiopoietin 1, activin A
3) Inhibition of fibrosis: hepatocyte growth factor (HGF), bFGF, adrenomedullin (ADM)
4) Inhibition of apoptosis: VEGF, HGF, IGF1, transforming growth factor (TGF) β, bFGF, granulocyte-macrophage colony-stimulating factor (GM CSF), activin A, thrombospondin 1. Immune-mediated effects include the following (5-8):
5) Suppression of T and B cells: Human leukocyte antigen G5 (HLA G5), HGF, inducible nitric oxide synthase (iNOS), indoleamine 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2), bFGF, TGFβ
6) Induction of differentiation and proliferation of regulatory T cells (Tregs) by TGFβ expression.
7) Inhibition of natural killer (NK) cells by secretion of IDO, PGE2, and TGFβ.
8) Inhibition of dendritic cell (DC) maturation by PGE2 secretion.
The figure "Stem Cell Res Ther" was reproduced by Carrión and Figueroa. May 11, 2011; 2(3):23.
Note: Red arrow...stimulation, black arrow...inhibition, unhooked arrow...direct inhibition
Abbreviation
iDC (immature dendritic cell), IL (interleukin), HGF (hepatocyte growth factor), TGF-β (transforming growth factor-β), PGE-2 (prostaglandin E2), IDO (indoleamine 2,3-dioxygenase), NO (nitric oxide), PD-L1 (programmed death ligand 1), hMSC (human mesenchymal stem cell), Treg (T regulatory), Th (T helper), CTL (cytotoxic T cell), mDC (mature dendritic cell), PD-1 (programmed cell death protein 1), PMN (polymorphonuclear leukocyte), NK (NK cell)
Localized uptake within the anterior ventricular region of the animal heart
These are sagittal (left) and coronal (right) views of fused SPECT/CT images from day 1 (a), day 2 (b), and day 7 (c). At the last imaging point (days 5-8), the apical region of MSC ingestion (arrow) is shown in the coronal structure diagram for three representative animals.
The distal peak distribution persisted independently of whether an initial focal hotspot was detected. (Indicated by the yellow arrow in (f))
Biological Characteristics of Isolated Bone Marrow Stromal Cells (BMSCs)
Cells were cultured from bone marrow after density fractionation, and are shown as (A) 48 hours after plating and (B) 10 days after plating. (C) Fluid cell counting shows the enrichment of these cultured cells.
Results were evaluated on days 2, 5, and 14 of culture, utilizing the SH2 and SH3 monoclonal antibodies raised against specific surface markers. (11)
By day 14, the cell population achieved 95–99% homogeneity, testing negative for the pan-hematopoietic antigens CD14, CD34 (Becton-Dickinson), and CD45 (Pharmingen). (D) The homogeneity and reproducibility of the isolation protocol were rigorously validated via flow cytometry.
