Table 2.
Adipose-derived stem cells’ secretome investigations for cell-free therapy.
| Paracrine Factors | Model | Therapeutic Effect | References |
|---|---|---|---|
| Neurodegenerative Diseases | |||
| BDNF, GDNF | Mouse Parkinson disease model | Protection of dopaminergic neurons. | [128] |
| Exosomes | Mice Alzheimer disease Model | Reduction of amyloid beta (Aβ) levels and the Aβ42/40. Increasing cell survival and decrease of neuronal death in the hippocampus and the cerebral cortex. Decrease deposition of Aβ plaques in Alzheimer Disease by exosomal neprilysin. |
[134,135] |
| Exosomes | Mice-derived neural cells from Huntington’s disease mouse model | Reduction of accumulation of mHtt aggregates, mitochondrial dysfunction and cell apoptosis by p-CREB-PGC1α pathway activation in Huntington’s disease. | [136] |
| Exosomes | Mice-derived neuronal cells from Amyotrophic lateral sclerosis disease mouse model | Reduction of cytosolic superoxide dismutase 1 and restore of the abnormal reduction of mitochondrial proteins. | [137] |
| Exosomes | Mouse progressive Multiple Sclerosis model | Brain atrophy reduction and remyelination promotion. Reduction of Th1 and Th17 levels. |
[138] |
| Exosomes | Brain injured male Sprague-Dawley rats | Reduction of inflammatory indicator (Ly6G+/CD11b/c+) and immune (CD3+/CD4+/CD3+/CD8+) cells. Reduction of early and late apoptotic cells. |
[31] |
| Exosomes (containing or depleted of MALAT1) |
Rats following a mild controlled cortical impact | Modulation of inflammation-related after traumatic brain injury by MALAT1. | [139] |
| Cardiovascular diseases | |||
| Exosomes | Endothelial cells | Promotion of vascularization by overexpressing miR-21. | [30] |
| VEGF | Human microvascular endothelial cells and mouse Hindlimb Ischemia model |
Reduction of endothelial cells apoptosis. Perfusion improvement in ischemic hindlimbs. |
[95] |
| IGF-1, BDNF | Cerebellar granule neurons | Blocking postischemic p38 activation. Protection of neural cells. |
[140] |
| Exosomes | Rat Acute Ischemic Stroke model | Increase of neural regeneration. Reduction of brain infarct zone, brain swelling, and shrinkage. |
[144] |
| Exosomes released by PDGF-stimulated adipose-derived stem cells | Acute Hindlimb Ischemia mouse model | Muscle protection from Acute Ischemia. | [145] |
| Engineered modified exosomes encoding VEGF | Nude mouse fat transplantation model | Improvement of neo-angiogenesis and vascularization by promoting cell proliferation and vascular maturity. | [143] |
| Exosomes | Vascular endothelial cells and nude mice transplantation model |
Promoting exogenous angiogenesis. Increase the proliferation, migration, tube formation, and VEGF secretion. Improving the survival of fat grafts. |
[142] |
| Metabolic diseases | |||
| PDGF | Diabetic patients adipose-derived stem cells and SCID Wound mice model |
Increased proliferation, migration, and homing to sites of inflammation. | [151] |
| Exosomes | Diabetic rat model | Restored erectile function due to corin content in exosomes. | [154] |
| Exosomes | Mouse podocyte MPC5 cells and spontaneous diabetes mice |
Reducing high glucose-induced increase of cell death. Reduction of urine protein, serum creatinine, blood urea nitrogen, and podocyte apoptosis. |
[156] |
| Exosomes (miR-26a-5p) |
Mouse podocyte MPC5 cells and spontaneous diabetes mice |
Protection of cells from injury. Protection against diabetic nephropathy. |
[157] |
| Exosomes | Peritoneal macrophages and obesity mouse model |
Improving obesity-related inflammation and metabolism. | [60] |
| Exosomes | Sepsis-induced acute kidney injury mouse model | Renal Protective effect in acute kidney injury. | [158] |
| Respiratory diseases | |||
| HGF | Pulmonary emphysema rat model | Increased alveolar and vascular repair. | [161] |
| Artifical Nanovesicles | MLE-12 epithelial cells and elastase-induced emphysema mice |
Proliferation increase. Inhibition of emphysema primarily by an FGF2-dependent pathway. |
[162] |
| Exosomes | Histone-induced acute lung injury mice | Improvement of survival. Inhibition histone-mediated lung hemorrhage edema, Reduction of vascular hyper-permeability. |
[80] |
| Skeletal tissue regeneration | |||
| Exosomes | Adipose-derived stem cells | Induction of osteogenic differentiation. | [166] |
| Exosomes | Synovial fibroblasts and periosteal cells | Chondrogenesis promotion. Increased Collagen type II and β-catenin expression. Increased proliferation (miR-145) and chondrogenic potential (miR-221). |
[167] |
| Conditioned Media | Osteoarthritic mice model | Rapid and lasting pain relief. No effect on tissue regeneration. |
[153] |
| Exosomes | Chondrocytes from osteoarthritic patients | Reduction of MMP-1, MMP-3, MMP-13 and ADAMTS-5. Increased collagen II expression. |
[169] |
| Exosomes | Chondrocytes from osteoarthritic patients | Reduction of MMP-3 expression. Increased collagen II expression. |
[168] |
| Whole secretome/isolated exosomes | Mouse myoblast cell line C2C12 and C57BL/6 mice |
Increased cell proliferation, skeletal muscle differentiation and migration. Enhancing of regeneration of skeletal muscle in acute damage. |
[165] |
| Exosomes | Massive rotator cuff tear rat model | Prevention of atrophy, fatty infiltration, inflammation, and vascularization of muscles. | [170] |
| Wound healing and skin aging | |||
| Platelet-rich plasma and conditioned Media | Fibroblasts and keratinocytes isolated from skin sample | Increased cell proliferation and migration. | [172] |
| Conditioned Media | Human epidermal keratinocyte neonatal cells | Acceleration of keratinocyte differentiation via miR-24 upregulation. | [173] |
| Exosomes | Human keratinocyte cell line HaCaT | Increased migration and proliferation by exosomal miR-21. Enhancing MMP-9 expression. Promotion of wound healing. |
[176] |
| Exosomes | Human keratinocyte cell line HaCaT | TGF-β pathway regulation by miR-19b. Promotion of wound healing. |
[79] |
| Exosomes | Human keratinocyte cell line HaCaT | Promotion of wound healing via Wnt/β-catenin pathway. Increased proliferation and migration. Apoptosis inhibition. |
[78] |
| Conditioned media | Human keratinocyte cell line HaCaTs and normal human dermal fibroblasts |
Anti-photoaging activity. Reduced IL-6 secretion. |
[183] |
| Engineered modified exosomes miR-21-5p | Human keratinocyte cell line HaCaT and fullthickness skin defects diabetic rat model |
Promotion of wound healing via Wnt/β-catenin pathway. Improved wound healing by re-epithelialization, collagen remodeling, angiogenesis, and vessel maturation. |
[178] |
| Conditioned Media | Ischemia/reperfusion flap mice model | Increased cell proliferation and the number of hair follicles. Prevention from flap necrosis after skin flap transplantation. |
[174] |
| Exosomes | Human umbilical vein endothelial cell | Reduction of inflammation and apoptosis. Enhancing skin flap recovery. |
[175] |
| Exosomes | Human embryonic kidney 293 cells | Prolonged the survival of vascularized composite allografts after transplantation. Downregulation of CD4 + T and Th1 cells. Upregulation Tr1 and Treg cell. |
[32] |
| Conditioned media | Human dermal fibroblasts | Reduced cellular senescence of skin cells. Improved collagen I, collagen III, elastin, and TIMP-1 expression. |
[182] |
| Exosomes | Atopic dermatitis mouse model | Decreased level of IgE and eosinophiles in blood and CD86+ and CD206+ cells in skin lesion. Reduction of (IL)-4, IL-23, IL-31. |
[179] |
| Exosomes | Chronic allergic dermatitis mouse model | Promotion of epidermal barrier repair. Reduction of IL-5, IL-13, TNF-α, IFN-γ, IL-17, and TSLP. |
[180] |