Prospect of Stem Cell Conditioned Medium in Regenerative Medicine

Table 1

Studies on various subjects, conditions, source of conditioned medium, and outcome.

Condition/disease	Subject	Source of conditioned medium	Outcome	Reference number
Alopecia—ID	Human	Hu-AD-MSC	Increased hair growth	[3]
Bald—SC	C3H/HeN nude mice	Hu-AD-SC	Hair growth	[5]
Acute hind limb ischemia—direct IM	Female athymic mouse	Hu-AD-SC	Decreased LL and F; Increased BF, angiogenesis, endothelial growth, homing, and AA	[6]
	SCID mice	Hu-ESC—endothelial cells	Vascularization and BF: CM restored defective diabetic PB derived PAC	[7]
Chronic hind limb ischemia—7–10 days IM	Male nude athymic	Hu-PB-MNC-EPC; Hu-UC-HUVEC	Increased hind limb BF	[8]
	Male NOD-SCID mouse	Hu-AF—SC—Ckit (+)	Increased arteriogenesis, capillary density, total perfusion area, and mobility, and decreased muscular deg	[9]
Skin wound direct—ID, [11] SC [10, 12]/topical application [4, 13]	Human	Hu-AD-SC	Enhanced wound healing; Reduced adverse effects	[4]
	BALBc nude mice	(i) Hu-UCB-MNC UCB-SC; (endothelial + MSC); (ii) HUVEC	Faster wound healing: UCB-SC was better than HUVEC	[10]
	Diabetic immunodeficient mice	Hu-UCB-CD34-EPC	Faster wound closure; Less granulation tissue area; More neovascularization	[11]
	Male db/db (diabetic) mice	Hu-UC-MSC	Faster wound closure; Increased capillary density	[12]
	BALBc-nude mouse	(i) Hu-ESC—derived EPC; (ii) Hu-UCB-EPC	Faster wound healing, granulation, and reepithelization: huESC-EPC was better than UCB-EPC	[13]
Skin wound—48 hour after wound—SC	Male NOD-SCID mice	Hu-BM-MSC	Faster wound healing	[14]
MCI—direct—peri-infarct injection	Male SCID or C57BL/6 mouse	Hu-AD-SC	Improved cardiac function; Reduced infarct size; Effect of huAD-SC > CM	[1]
MCI—end of 2nd hour R—IC	Female L pig	Porcine PB-EPC	Reduced IZ-A and infarct size; Increased IZ angiogenesis; IZ cardiomyocyte hypertrophy; Improved LV contractility and; relaxation	[15]
MCI—4 hours—IV (jugular vein)	DL pig	Hu-ESC-MSC	Increased capillary density; Reduced infarct size; Preserved S-D performance	[16]
MCI—48 hours-IM yo	Rat nude athymic	Hu-BM-derived MPC	Improved LV function; Reduced LV dilation, myocyte A, and fibrosis; Increased neovascularization	[17]
MCI—5 min before R—IV, -at R—IC	Female DL pig	Hu-ESC derived MSC	(i) Reduced infarct size and A; (ii) Improved S-D performance	[18]
MCI—5 min before R—IV—(tail)	Mouse	Hu-ESC derived MSC	Reduced infarct size; (>1000 kD/100–220 nm) = 10–220 nm < 10–100 nm
RSLT—direct—IV—(penile)	Male SD rat	Rat BM-MSC	Reduced LIB and PIC; Increased survival	[19]
Acute hepatic failure—24 hours—intrahepatic (left liver lobe)	CCl4 injured SCID/NOD mice	1-Hu-AF MSC; 2-AF-MSC-hepatic progenitor-like cells (HPL)	(i) AST, ALT decreased; (ii) Liver phenotype improvement; HPL was better than MSC-CM	[20]
Fulminant hepatic failure—24 hours—IV (penile)	Male SD rat	Hu-MSC	Reduced ALT, AST, TNF, IL6, and IL1-rec-A level, and HP, ICI, and A; Increased IL10 level, liver regeneration, and survival	[21]
	Male SD rat	Hu-BM-MSC	Reduced panlobular leucocyte infiltrate, hepatocellular death, and bile duct duplication and increased survival	[22]
Focal cerebral ischemia—72 hours—intranasal	Male SD rat	(i) Hu-SC-EDT; (ii) BM-MSC (Lonza)	Increased migration-diff—endogenous NPC, vasculogenesis, and motor function, and reduced infarct size; (Hu SC-EDT = BM-MSC)	[23]
Ischemic stroke—after 8 days—lateral ventricle infusion	Male SD mice	Hu-AD-MSC	Motor function maintained, reduced infarct volume, neural cell A, and astrogliosis, and increased microvessel	[24]
Cerebral ischemia infarction—1 day—IC/intracardiac (LV) injection	immunodeficient mice	(i) Hu-BM-MSC; (ii) Hu-BM-CD133; (iii) Hu-BM-p75; (iv) Hu-fibro	Reduced cortical infarct volume; (huBM-CD133-CM < huBM-MSC-CM < hufibroCM < huBM-p75CM)	[25]
Fluid percussion-TBI—direct IV jugular vein	Male SD rat	Hu-BM-MSC	Reduced neuron loss, A, neuron A, infarction volume, and motor deficit; Increased VEGF(+) cells	[26]
Fluid percussion TBI—12 hours after—IV	Male SD rat	Hu-BM-MSC	Decreased brain damage volume, brain damage incidence, and neuron A (hypoxia < normoxia); Increased motor/cognitive function and neurogenesis (hypoxia > normoxia)	[27]
Contusion spinal cord injury—direct	Female Wistar rat	Rat-BM-MSC	Increased motor recovery	[28]
Chronic kidney disease—week 5—IV (tail)	Male Le rat	Hu embryonic MSC—stable—80 population doublings	Decreased systolic BP, proteinuria, and tubular + glomerular damage; Increased inulin and PAH clearance, glomerular endothelium, and DNA repair	[29]
Nephropathy—24 hours—IV (tail)	Mouse BALBc	(i) Hu-UCB-USSC; (ii) Mouse BM-MSC	No improvement in serum urea and creatinine, HP, and physical activity score	[30]
Normal—cancer cell line + CM xenograft	BALB mice	Hu-MSC (cell line)	Increased tumor cell proliferation (PCNA) and vascularization	[31]
VILI—before induction—IV—(tail)	Male C57BL/6 mouse	Mouse-iPSC	Reduced tidal volume, and bronchial microstructure restored	[32]
Intrabony periodontal defect direct—implant	Hybrid dog	Hu-MSC (Lonza)	Increased alveolar bone and cementum regeneration	[33]

ID: intradermal, IM: intramuscular, SC: subcutaneous, MCI: myocardial infarct, R: reperfusion, IC: intracoronary artery, IV: intravenous, Imyo: intramyocardial, LV: left ventricular, RSLT: 50% reduced size liver transplantation, TBI: traumatic brain injury, VILI: ventilator induced lung injury, SCID: severe combined immunodeficient, NOD: nonobese diabetic, SD: Sprague-Dawley, DL: Dalland Landrace, L: Landrace, W: Wistar, Le: Lewis, hu: human, AD: adipose tissue derived, MSC: mesenchymal stem cells, SC: stem cell, ESC: embryonic stem cell, PB: peripheral blood, MNC: mononuclear cell, UC: umbilical cord, UCB: UC blood, BM: bone marrow, EPC: endothelial progenitor cell, HUVEC: human umbilical vein endothelial cell, AF: amniotic fluid, EDT: exfoliated deciduous tooth, MPC: mesenchymal progenitor cell, USSC: unrestricted somatic stem cell, iPSC: induced pluripotent stem cell, LL: limb lost, F: fibrosis, BF: blood flow, AA: antiapoptosis, CM: conditioned medium, PAC: proangiogenic cells, deg: degeneration, IZ: infarct zone, A: apoptosis, ALT: alanine amino transferase, AST: aspartate aminotransferase, HP: histopathology, ICI: immune cell infiltration, S-D: systolic-diastolic, LIB: liver injury biomarker, PIC: proinflammatory cytokine, Hu-SC-, IL1-rec-A: IL1 receptor antagonist, NPC: neural progenitor cell, PAH: para amino hippuric acid.