scholarly journals Gingiva-Derived Mesenchymal Stem Cells: Potential Application in Tissue Engineering and Regenerative Medicine - A Comprehensive Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Dane Kim ◽  
Alisa E. Lee ◽  
Qilin Xu ◽  
Qunzhou Zhang ◽  
Anh D. Le

A unique subpopulation of mesenchymal stem cells (MSCs) has been isolated and characterized from human gingival tissues (GMSCs). Similar to MSCs derived from other sources of tissues, e.g. bone marrow, adipose or umbilical cord, GMSCs also possess multipotent differentiation capacities and potent immunomodulatory effects on both innate and adaptive immune cells through the secretion of various types of bioactive factors with immunosuppressive and anti-inflammatory functions. Uniquely, GMSCs are highly proliferative and have the propensity to differentiate into neural cell lineages due to the neural crest-origin. These properties have endowed GMSCs with potent regenerative and therapeutic potentials in various preclinical models of human disorders, particularly, some inflammatory and autoimmune diseases, skin diseases, oral and maxillofacial disorders, and peripheral nerve injuries. All types of cells release extracellular vesicles (EVs), including exosomes, that play critical roles in cell-cell communication through their cargos containing a variety of bioactive molecules, such as proteins, nucleic acids, and lipids. Like EVs released by other sources of MSCs, GMSC-derived EVs have been shown to possess similar biological functions and therapeutic effects on several preclinical diseases models as GMSCs, thus representing a promising cell-free platform for regenerative therapy. Taken together, due to the easily accessibility and less morbidity of harvesting gingival tissues as well as the potent immunomodulatory and anti-inflammatory functions, GMSCs represent a unique source of MSCs of a neural crest-origin for potential application in tissue engineering and regenerative therapy.

2020 ◽  
Vol 21 (16) ◽  
pp. 5905
Author(s):  
Maria Camilla Ciardulli ◽  
Luigi Marino ◽  
Erwin Pavel Lamparelli ◽  
Maurizio Guida ◽  
Nicholas Robert Forsyth ◽  
...  

Mesenchymal stem cells derived from human bone marrow (hBM-MSCs) are utilized in tendon tissue-engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSCs), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to human Growth Differentiation Factor 5 (hGDF-5) we supplemented each at doses of 1, 10, and 100 ng/mL of hGDF-5 and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated the expression of collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis-A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed up-regulation of SCX-A (1.7-fold) at Day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX-A (3.8-fold) and TNC (2.3-fold) after three days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular-shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this, we explored the expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines up-regulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold), but a greater up-regulation of IL-10 (2.5-fold). Type 1 collagen and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification with a length/width ratio increase, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue-engineering protocols.


2019 ◽  
Vol 7 (7) ◽  
pp. 2861-2872 ◽  
Author(s):  
Xiuying Li ◽  
Zhenhong Wei ◽  
Binxi Li ◽  
Jing Li ◽  
Huiying Lv ◽  
...  

The Fe3O4@PDA NPs enhanced the recruitment of MSCs and improved the anti-inflammatory and healing ability compared with the MSC treatment alone.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaodong Geng ◽  
Quan Hong ◽  
Kun Chi ◽  
Shuqiang Wang ◽  
Guangyan Cai ◽  
...  

Background. The treatment of chronic kidney diseases (CKDs) by different approaches using mesenchymal stem cells (MSCs) has made great strides. In this study, we aimed to explore the potential mechanism of gelatin microcryogels (GMs) as a cell therapeutic vector to block the progression of CKD. Methods. In vivo, the pedicled omentum valve with MSC-loaded GMs was packed onto 5/6 nephrectomized kidneys derived from rats. The therapeutic effects were evaluated. In vitro, TNF-α, TGF-β, and MSCs were added to the medium of the HK-2 cell culture system, and key genes involved in anti-inflammatory and antifibrosis effects were evaluated by qPCR. Results. After 12 weeks of MSC transplantation, kidney functions, such as serum creatinine, urea nitrogen, and 24-hour urine protein, were significantly improved. The pedicled omentum valve was packed with MSC-loaded GMs onto the 5/6 nephrectomized kidney, and the expressions of collagen IV, α-SMA, and TGF-β were all evaluated by immunohistochemical staining and western blot analysis. MSC-loaded-GMs also showed antifibrotic effects by inducing the upregulation of HO-1, BMP-7, and HGF and the downregulation of MCP-1 at the mRNA level. Four weeks after MSC-loaded GM treatment, we found that the mRNA levels of TNF-α and IL-6 were clearly reduced. MSC-conditional medium (MSC-CM) showed that the TNF-α-induced expression of IL-8 and IL-6 mRNA was reversed; E-cadherin mRNA was upregulated; and the TGF-β-induced expression of collagen IV, α-SMA, and fibronectin (FN) mRNA in HK-2 cells was reduced. Conclusions. We demonstrated that the pedicled omentum valve packed with MSC-loaded GMs had a renal protective effect on the 5/6 nephrectomized kidney by observing the anti-inflammatory and antifibrosis effects.


Author(s):  
Maria Camilla Ciardulli ◽  
Luigi Marino ◽  
Erwin P. Lamparelli ◽  
Maurizio Guida ◽  
Nicholas R. Forsyth ◽  
...  

Mesenchymal Stem Cells derived from bone marrow (hBM-MSCs) are utilized in tendon tissue‐engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSC), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to hGDF-5 we supplemented each at doses of 1, 10, and 100 ng/mL and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated expression of Collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed upregulation of SCX-A (1.7-fold) at day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX (3.8-fold) and TNC (2.3-fold) after 3 days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this we explored expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines upregulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold) but a greater up-regulation of IL-10 (2.5-fold). Collagen type I and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification (fibroblast-like) with a Lenght/Width ratio increase at value higher than 1, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue engineering protocols.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hyunjeong Kim ◽  
Gwanghyun Yang ◽  
Jumi Park ◽  
Jene Choi ◽  
Eunju Kang ◽  
...  

Abstract Osteoarthritis (OA) is a degenerative condition of the temporomandibular joint (TMJ) characterised by chronic inflammation and damage to joint structures. Because of the complexity of TMJ-OA, only symptomatic treatments are currently available. Recent reports have shown that many of stem cells can exert anti-inflammatory and tissue-regenerating effects. In this study, we investigated the potential cartilage-regenerating and anti-inflammatory effects of human umbilical cord matrix-mesenchymal stem cells (hUCM-MSCs) for the treatment of TMJ-OA. hUCM-MSC lines, isolated from different donors, which showed different activities in vitro. Using a selected cell line, we used different concentrations of hUCM-MSCs to assess therapeutic effects in a rabbit model of monosodium iodoacetate-induced TMJ-OA. Compared with the untreated control group, the potential regenerative result and anti-inflammatory effects of hUCM-MSCs were evident at all the tested concentrations in rabbits with induced TMJ-OA. The median dose of hUCM-MSCs showed the prominent cartilage protective effect and further cartilage regeneration potential. This effect occurred via upregulated expression of growth factors, extracellular matrix markers, and anti-inflammatory cytokines, and reduced expression of pro-inflammatory cytokines. The anti-inflammatory effect of hUCM-MSCs was comparable to that of dexamethasone (DEX). However, only hUCM-MSCs showed potential chondrogenesis effects in this study. In conclusion, our results indicate that hUCM-MSCs may be an effective treatment option for the treatment of TMJ-OA.


Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2046
Author(s):  
Huey-Shan Hung ◽  
Mei-Lang Kung ◽  
Fang-Chung Chen ◽  
Yi-Chun Ke ◽  
Chiung-Chyi Shen ◽  
...  

Graphene-based nanocomposites such as graphene oxide (GO) and nanoparticle-decorated graphene with demonstrated excellent physicochemical properties have worthwhile applications in biomedicine and bioengineering such as tissue engineering. In this study, we fabricated gold nanoparticle-decorated GO (GO-Au) nanocomposites and characterized their physicochemical properties using UV-Vis absorption spectra, FTIR spectra, contact angle analyses, and free radical scavenging potential. Moreover, we investigated the potent applications of GO-Au nanocomposites on directing mesenchymal stem cells (MSCs) for tissue regeneration. We compared the efficacy of as-prepared GO-derived nanocomposites including GO, GO-Au, and GO-Au (×2) on the biocompatibility of MSCs, immune cell identification, anti-inflammatory effects, differentiation capacity, as well as animal immune compatibility. Our results showed that Au-deposited GO nanocomposites, especially GO-Au (×2), significantly exhibited increased cell viability of MSCs, had good anti-oxidative ability, sponged the immune response toward monocyte-macrophage transition, as well as inhibited the activity of platelets. Moreover, we also validated the superior efficacy of Au-deposited GO nanocomposites on the enhancement of cell motility and various MSCs-derived cell types of differentiation including neuron cells, adipocytes, osteocytes, and endothelial cells. Additionally, the lower induction of fibrotic formation, reduced M1 macrophage polarization, and higher induction of M2 macrophage, as well as promotion of the endothelialization, were also found in the Au-deposited GO nanocomposites implanted animal model. These results suggest that the Au-deposited GO nanocomposites have excellent immune compatibility and anti-inflammatory effects in vivo and in vitro. Altogether, our findings indicate that Au-decorated GO nanocomposites, especially GO-Au (×2), can be a potent nanocarrier for tissue engineering and an effective clinical strategy for anti-inflammation.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Jihye Kwak ◽  
Soo Jin Choi ◽  
Wonil Oh ◽  
Yoon Sun Yang ◽  
Hong Bae Jeon ◽  
...  

Human mesenchymal stem cells (hMSCs), including human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs), which have high proliferation capacity and immunomodulatory properties, are considered to be a good candidate for cell-based therapies. hMSCs show enhanced therapeutic effects via paracrine secretion or cell-to-cell contact that modulates inflammatory or immune reactions. Here, treatment with cobalt chloride (CoCl2) was more effective than naïve hUCB-MSCs in suppressing inflammatory responses in a coculture system with phytohemagglutinin- (PHA-) activated human peripheral blood mononuclear cells (hPBMCs). Furthermore, the effect of CoCl2 is exerted by promoting the expression of anti-inflammatory mediators (e.g., PGE2) and inhibiting that of inflammatory cytokines (e.g., TNF-α and IFN-γ). Treatment of hUCB-MSCs with CoCl2 leads to increased expression of microRNA- (miR-) 146a, which was reported to modulate anti-inflammatory responses. Hypoxia-inducible factor- (HIF-) 1α silencing and ERK inhibition abolished CoCl2-induced miR-146a expression, suggesting that ERK and HIF-1α signals are required for CoCl2-induced miR-146a expression in hUCB-MSCs. These data suggest that treatment with CoCl2 enhances the immunosuppressive capacity of hUCB-MSCs through the ERK-HIF-1α-miR-146a-mediated signaling pathway. Furthermore, pretreatment of transplanted MSCs with CoCl2 can suppress lung inflammation more than naïve MSCs can in a mouse model of asthma. These findings suggest that CoCl2 may improve the therapeutic effects of hUCB-MSCs for the treatment of inflammatory diseases.


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