Table 3.
In vitro studies of UC-MSCs or their secretome.
| Study type | Source | Aim | Culture system | Results | Ref. |
|---|---|---|---|---|---|
| Chondrogenic differentiation | Human UC-MSCs | UC- and AT-MSC comparison | Cultured in CM supplemented with TGFβ3 and BMP-6 | A more fibrous than hyaline cartilage phenotype in UC-MSCs compared to AT-MSCs | Hildner et al., 2010 [87] |
| Human WJ-MSCs | Differentiation into NP-like cells | Coculture with NPCs | Increased expression of aggrecan, collagen II, and SRY-type HMG box-9 genes | Ruan et al., 2012 [88] | |
| Human UC-MSCs | Differentiation into NP-like cells | Cultured in a laminin-rich pseudo-3D culture system | GAGs, collagen II, laminin α5, and laminin receptors (integrin α3 and β4) expression | Chon et al., 2013 [89] | |
| Human WJ-MSCs | Immunomodulatory properties test | Cultured in CM | Differentiated WJ-MSCs maintain their immune privilege | La Rocca et al., 2013 [50] | |
| Human UC-MSCs | Elastic cartilage differentiation | Seeded on PLGA nanofiber scaffolds with CM and CTGF | Increase of GAG/DNA ratio, collagen II, elastin mRNA and protein. No difference in collagen X or fibrillin mRNA | Caballero et al., 2013 [90] | |
| Human UC-MSCs | Tissue-engineered (TE) elastic cartilage from UC-MSCs and human cartilage comparison | Seeded onto PLGA nanofiber scaffolds with CM supplemented with CTGF | TE elastic cartilage from UC-MSCs expresses embryonic fibrillin III and similar levels of elastin, fibrillin I, collagens I and X when compared to native cartilage. | Pappa et al., 2014 [120] | |
| Human and porcine UC-MSCs | Effects of periodic vibratory stimulus on UC-MSC differentiation | Cultured in chondrogenic or osteogenic medium and exposed to 1 or 100 Hz frequency vibrations | 1 Hz stimulation resulted in a cartilage phenotype while 100 Hz stimulation resulted in a bone phenotype for both human and porcine UC-MSCs | Cashion et al. 2014 [121] | |
| Human UC-MSCs | UC-, BM-, and AT-MSC chondrogenesis comparison | Cultured in CM | Slightly differences in chondrogenesis between the MSCs. BM-MSCs showed the best chondrogenic potential | Danišovič et al., 2016 [92] | |
| Human UC-MSCs | Effect of mechanical compression on UC-MSC chondrogenesis | Seeded in PVA-PCL scaffold with CM and subjected to dynamic compression | Increase in chondrogenic differentiation | Remya et al., 2016 [122] | |
| Human WJ-MSCs | Simulation of the articular cartilage microenvironment | Coculture of WJ-MSCs and primary ACs in ACECM- oriented scaffold | Chondrogenic differentiation of WJ-MSCs without any inducer, hyaline cartilage phenotype, and improved cytoactivity of ACs | Zhang et al., 2019a [96] | |
| Human UC-MSCs | Interactions between ACs and UC-MSCs. | Coculture with direct cell-cell contact | Enhanced differentiation of UC-MSCs and reduced dedifferentiation of chondrocytes | Li et al., 2019 [97] | |
| WJ-MSCs | Immunomodulatory properties test | Chondrogenic differentiation in Alg/HA scaffold | Differentiated WJ-MSCs inhibit T cell alloproliferation and maintain paracrine activity and functional immunomodulation | Voisin et al., 2020 [84] | |
| Cartilage tissue engineering | Human UC-MSCs | PGA and PLLA scaffolds comparison | Seeded on nonwoven PGA or PLLA scaffolds in CM | Similar chondrogenic potential of UC-MSCs in PLLA and PGA scaffolds. | Zhao et al., 2010 [123] |
| Human WJ-MSCs | WJ- and BM-MSCs chondrogenesis comparison | Seeded in PCL/Coll nanofibrous scaffolds in CM | Enhanced cell attachment, proliferation, and chondrogenesis of WJ-MSCs over BM-MSCs | Fong et al., 2012 [124] | |
| Human UC-MSCs | Chondrogenic differentiation | Embedded in collagen hydrogel scaffold with CM | Increased expressions of collagen II, aggrecan, COMP, and sox9 | Chen et al., 2013 [125] | |
| Human UC-MSCs | Chondrogenic differentiation in PVA-PCL scaffolds | Seeded in PVA-PCL scaffolds with individual TGFβ1, TGFβ3, IGF, BMP2 and their combination with BMP2 | SOX9, collagen II and aggrecan expression. The combination TGF-β3 and BMP-2 was the more effective for chondrogenesis | Nirmal et al., 2013 [126] | |
| Human WJ-MSCs | Fabrication of a nonscaffold tissue-engineered cartilage | Pellet culture combined with RCCS | RCCS formed larger and condenser cartilage-like tissue enriched of GAGs and collagen II than pellet culture | Liu et al., 2014 [12] | |
| Human WJ-MSCs | WJ- and BM-MSCs chondrogenesis in agarose hydrogel | Encapsulation of WJ-MSCs or BM-MSCs aggregates in agarose hydrogels | Both BM-MSCs and WJ-MSCs did better in matrix biosynthesis and chondrogenesis when in aggregates than in free cell suspension | Sridharan et al., 2015 [127] | |
| Human UC-MSCs | Chondrogenic differentiation in SF/HA scaffold | Seeded in different ratios of SF/HA with CM | Expression of collagen II, aggrecan, and Sox9. SF80 and SF70 scaffolds are the best for chondrogenesis | Jaipaew et al., 2016 [128] | |
| Human WJ-MSCs | Chondrogenesis of WJ-MSCs in PLLA-collagen nanofibers scaffold | Seeded on PLLA-collagen nanofibers scaffold with CM | PLLA-collagen nanofibers scaffold promotes the chondrogenic differentiation of WJ-MSCs | Wang et al., 2017 [129] | |
| Human WJ-MSCs | Chondrogenesis of WJ-MSCs in hyaluronic acid-based hydrogels | Seeded in hyaluronic acid-based hydrogels with CM | Increase of GAGs, collagen II and aggrecan, | Aleksander-Konert et al., 2016 [130] | |
| Human UC-MSC- ECM | Effect of decellularized UC-MSC-ECM on ACs | ACs seeded in culture plates coated with UC-MSC-ECM | Promotion of the proliferation and differentiation of chondrocytes | Zhang et al., 2019b [131] | |
| Fibrocartilage tissue engineering | Human UC-MSCs | UC- and BM-MSCs chondrogenesis comparison | Seeded onto PGA scaffolds in chondrogenic medium | More GAGs, collagen I, and aggrecan and less collagen II in UC-MSCs than BM-MSCs | Wang et al., 2009a [132] |
| Human UC-MSCs | Best density for UC-MSCs chondrogenesis | Seeded on nonwoven PGA scaffold in CM | More collagen I and II, aggrecan, GAGs, and mechanical integrity in high-density groups | Wang et al., 2009b [133] | |
| Osteochondral tissue engineering | Human UC-MSCs | Chondrogenic and osteogenic differentiation | Seeded between chondrogenic and osteogenic PLLA constructs | Both chondrogenic and osteogenic differentiation of UC-MSCs in the respective sides of constructs | Wang et al., 2011 [134] |
| Human UC-MSCs | Chondrogenic and osteogenic differentiation | Seeded in osteogenic scaffold and in Collagen I and III- or HA-based chondrogenic scaffolds in normoxic or hypoxic (8% O2) conditions. | Both chondrogenic and osteogenic differentiation of UC-MSCs. Hypoxia improved the expression of these chondrogenic markers | Marmotti et al., 2017 [31] | |
| Orthopaedic tissue engineering | Human UC-MSCs | Multilineage differentiation | Cultured in adipogenic, osteogenic, chondrogenic, or myogenic medium | Multilineage differentiation potential toward bone, fat, cartilage, and muscle | Marmotti et al., 2012 [91] |
| IVD degeneration | Human UC-MSCs | UC- and D-NP-MSCs comparison | Cultured with CM | D-NPMSCs expressed lower expression levels of CD29 and CD105, reduced proliferation capability and differentiation potentials | Wu et al., 2017 [93] |
| Human WJ-MSCs | Interactions between WJ-MSCs and degenerative NPCs | Coculture with or without direct cell-cell contact | NP-like cell differentiation of WJ-MSCs and biological status of degenerative NPCs restoration. The direct cell-cell contact yielded more favorable gene expressions | Han et al., 2018 [98] | |
| Human UC-MSCs secretome | UC-MSC-conditioned medium (CM) effect on damaged NP-MSCs | Treatment of high glucose-induced degradation of NP-MSCs with UC-MSCs-CM | Reduction of apoptosis and ECM degradation via the p38 MAPK pathway | Qi 2019 et al., 2019 [135] | |
| Human UC-MSCs-ECM | Effect of UC-MCS-ECM on IVD cells | IVD cells seeded on decellularized UC-MSCs-ECM | UC-MSCs-ECM improved the degenerated phenotype of human IVD cells affecting the expression of Sox2, Sox 9 and TRPS1 | Penolazzi et al., 2020 [136] | |
| OA | Human UC-MSCs secretome | Comparison of articular cartilage (AC), Hoffa's fat pad (HFP), synovial membrane (SM), and UC-MSC secretomes | Secretome analysis by mass spectrometry and effect on AC chondrogenesis and immunosuppressive and anti-inflammatory effects on PBMCs and macrophages | UC-MSCs-CM displayed superior anti-inflammatory, immunomodulatory and trophic effects compared to adult MSCs | Islam et al., 2019 [95] |
| RA | Human UC-MSCs | UC-MSCs effect on FLS | Coculture | Increase of FLS apoptosis, collagen II, and aggrecan; decrease of IL-1β, IL-6 and CCL-2 | Zeng et al., 2016 [61] |
| TMJ disorders | Human UC-MSCs | UC-MSCs and TMJ condylar chondrocytes comparison | Seeded in PGA scaffolds in CM | More collagen I and II, GAGs, and cellular density in UC-MSCs than TMJ construct | Bailey et al., 2007 [94] |
AC: articular cartilage cells; ACECM: acellular cartilage extracellular matrix; Alg/HA: alginate enriched in hyaluronic acid; CTGF: connective tissue growth factor; CM: chondrogenic medium; D-NP-MSCs: NP stem/progenitor cells isolated from degenerated IVD; ECM: extracellular matrix; FLS: fibroblast-like synoviocytes; GAGs: glycosaminoglycans; n.a.: not applicable; IVD: intervertebral disc; NP: nucleus pulpous; NPCs: nucleus pulposus cells; OA: osteoarthritis; PCL/Coll: polycaprolactone/collagen; PGA: polyglycolic acid; PLGA: poly L-lactide/D-lactide/glycolide; PLLA: poly-L-lactic acid; PMEF: pulsed electromagnetic field; PVA-PCL: polyvinyl alcohol-polycaprolactone; RA: rheumatoid arthritis; RCCS: rotary cell-culture system; SF/HA: silk fibroin/hyaluronic acid; TMJ: temporomandibular joint.