Review Article

Functional Properties of Human-Derived Mesenchymal Stem Cell Spheroids: A Meta-Analysis and Systematic Review

Table 3

In vivo therapeutic effect of MSC spheroids.

Source of MSCTherapeutic effectAnimal study model
In vivo main findings

Bone marrow (ref)
21Higher anti-inflammatory effect, 3D versus 2D, (spheroid treatment decreased neutrophil activity, and TNF-a, IL-1b, CXCL2/MIP2 and PGE2 levels.Murine zymosan-induced peritonitis.
34Ambient conditions-recovered MSC retains therapeutic effect (3D versus 2D).DSS and TNBS-induced mouse colitis model.
39High anti-inflammatory effect (enhanced PGE-2 and IL-10 and decreased TNF-a levels).LPS-induced systemic inflammation in mice.
Adipose tissue
29Enhanced wound healing (faster wound closure, 3D versus 2D), higher production of tenascin C, collagen VI a3, fibronectin, MMP2, MMP14 and HGF.Diabetic mouse wound model.
51High therapeutic effect. Higher cellular retention after intramuscular injection into hindlimbs (3D versus 2D).Nude mice model.
18Higher regenerative capacity (3D versus 2D).Enhanced cutaneous wound closure, cell engraftment and angiogenesis.Wound healing nude mice model.
49Enhanced therapeutic and regenerative effect (3D versus 2D). Greater regeneration of lung tissues and higher FGF2 and HGF expression.Elastase-induced emphysema mouse model.
45Higher cell survival and proliferation in ischemic tissue (3D versus 2D).Murine hindlimb ischemia model.
52Enhanced therapeutic and regenerative effect (3D versus 2D). Spheroids promoted tissue repair and reduced the final atrophy.Ischemia-reperfusion injury in SCID mice.
47Enhanced survival and therapeutic effect (3D versus 2D). Higher survival, angiogenic efficacy and differentiation into epithelial cells. Greater effectiveness in functional recovery of ischemic skin flap.Murine ischemic skin flap model.
37Enhanced survival, paracrine secretion and therapeutic effect (3D versus 2D). Higher secretion of VEGF, HGF and TSG-6. Less apoptosis and tissue damage at injury site and higher vascularization.Ischemia-reperfusion injury in rats kidneys.
Umbilical cord
33High regenerative and therapeutic effect (3D versus 2D). Enhanced cell survival, angiogenesis and cell adhesion molecules and growth factors expression (VEGF, FGF2, ICAM, VCAM and NG2). Spheroids transplantation improved limb salvage and attenuated fibrosis.Mouse hindlimb ischemia model.
50Enhanced regenerative and therapeutic effect (3D versus 2D). Faster decreased of ALT, AST and total bilirubin. Spheroid treatment increases IFN-g and IL-6 serum levels and reduces TNF-a levels.CCl4-induced acute liver failure murine model.
41Higher therapeutic effect of conditioned medium (3Dversus 2D), spheroid-derived conditioned medium attenuated tissue destruction, reduced synovial inflammation and bone erosion.Adjuvant-induced arthritis in wistar rats.