Dental Pulp Mesenchymal Stem Cells Promote Polarization of M2 Macrophages and Accelerate Wound Healing by Secreting CCL2

2021 ◽  
Author(s):  
Zi Yang ◽  
Linsha Ma ◽  
Congling Du ◽  
Jinsong Wang ◽  
Chunmei Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Tissue Regeneration ◽  
Dental Pulp ◽  
M2 Macrophages ◽  
Cell Sheets ◽  
Regeneration Potential ◽  
Macrophages Polarization

Abstract Background Mesenchymal stem cells (MSCs) are widely used in tissue engineering owing to their regenerative potential and immunomodulatory capacity. The crosstalk between MSCs and the host immune function plays a key role in the efficiency of tissue regeneration. However, the difference in immunological modulation and tissue regeneration function between MSCs from different sources remains unclear. Methods Human mesenchymal stem cells derived from bone marrow (BMMSCs), periodontal ligament (PDLSCs), adipose (ADSCs), and dental pulp (DPSCs) were obtained and induced to form cell sheets under the condition of 20 ug/ml vitamin C. The MSC cell sheets carried by hydroxyapatite/tricalciumphosphate (HA/TCP) particles were transplanted subcutaneously into C57BL6 mice for 8 weeks. Histological analyses were performed to detect the tissue regeneration potential and macrophages polarization in vivo. Then, THP-1 macrophages were co-cultured with MSCs and quantitative real-time polymerase chain reaction, immunofluorescent staining, western blotting, and enzyme-linked immunosorbent assay were used to investigate the function and mechanism of MSCs on macrophages in vitro. Finally, a wound healing model of the palatal mucosa was performed to confirm the effect of MSCs on macrophages and tissue healing efficiency. Results Compared to PDLSCs, BMMSCs, and ADSCs, DPSCs exhibited greater tissue regeneration potential, with greater tissue volume, higher Ki67 expression, and less apoptosis in the regenerated tissue of wild-type C57BL6 mice. In addition, DSPCs triggered more M2 macrophages in the regenerated tissue than other MSCs. Our data showed that DPSCs exhibited higher expression levels of C-C Motif Chemokine Ligand 2 (CCL2), and specific blocking of CCL2 by neutralising antibodies can significantly inhibit the DPSCs-induced polarization of M2 macrophages. Finally, DPSCs transplantation promoted wound healing of the palatal mucosa and M2 macrophages polarization in vivo, which could be significantly impaired by CCL2 neutralising antibody. Conclusions Our data indicate that DPSCs exert better tissue regeneration potential and immunoregulatory function by secreting CCL2. These results suggest that CCL2 application can enhance MSC-mediated tissue regeneration or wound healing.

scholarly journals Platelet-Rich Plasma Improves the Wound Healing Potential of Mesenchymal Stem Cells through Paracrine and Metabolism Alterations

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Barbara Hersant ◽  
Mounia Sid-Ahmed ◽  
Laura Braud ◽  
Maud Jourdan ◽  
Yasmine Baba-Amer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Platelet Rich Plasma ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Dependent Manner ◽  
Safe Alternative

Chronic and acute nonhealing wounds represent a major public health problem, and replacement of cutaneous lesions by the newly regenerated skin is challenging. Mesenchymal stem cells (MSC) and platelet-rich plasma (PRP) were separately tested in the attempt to regenerate the lost skin. However, these treatments often remained inefficient to achieve complete wound healing. Additional studies suggested that PRP could be used in combination with MSC to improve the cell therapy efficacy for tissue repair. However, systematic studies related to the effects of PRP on MSC properties and their ability to rebuild skin barrier are lacking. We evaluated in a mouse exhibiting 4 full-thickness wounds, the skin repair ability of a treatment combining human adipose-derived MSC and human PRP by comparison to treatment with saline solution, PRP alone, or MSC alone. Wound healing in these animals was measured at day 3, day 7, and day 10. In addition, we examined in vitro and in vivo whether PRP alters in MSC their proangiogenic properties, their survival, and their proliferation. We showed that PRP improved the efficacy of engrafted MSC to replace lost skin in mice by accelerating the wound healing processes and ameliorating the elasticity of the newly regenerated skin. In addition, we found that PRP treatment stimulated in vitro, in a dose-dependent manner, the proangiogenic potential of MSC through enhanced secretion of soluble factors like VEGF and SDF-1. Moreover, PRP treatment ameliorated the survival and activated the proliferation of in vitro cultured MSC and that these effects were accompanied by an alteration of the MSC energetic metabolism including oxygen consumption rate and mitochondrial ATP production. Similar observations were found in vivo following combined administration of PRP and MSC into mouse wounds. In conclusion, our study strengthens that the use of PRP in combination with MSC might be a safe alternative to aid wound healing.

scholarly journals Perivascular-Derived Mesenchymal Stem Cells

2019 ◽  
Vol 98 (10) ◽  
pp. 1066-1072 ◽  
Author(s):  
V. Yianni ◽  
P.T. Sharpe
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dental Pulp ◽  
Molecular Mechanisms ◽  
Lineage Tracing ◽  
Specific Gene ◽  
Genetic Lineage ◽  
Differentiation Potential

Cells have been identified in postnatal tissues that, when isolated from multiple mesenchymal compartments, can be stimulated in vitro to give rise to cells that resemble mature mesenchymal phenotypes, such as odontoblasts, osteoblasts, adipocytes, and myoblasts. This has made these adult cells, collectively called mesenchymal stem cells (MSCs), strong candidates for fields such as tissue engineering and regenerative medicine. Based on evidence from in vivo genetic lineage–tracing studies, pericytes have been identified as a source of MSC precursors in vivo in multiple organs, in response to injury or during homeostasis. Questions of intense debate and interest in the field of tissue engineering and regenerative studies include the following: 1) Are all pericytes, irrespective of tissue of isolation, equal in their differentiation potential? 2) What are the mechanisms that regulate the differentiation of MSCs? To gain a better understanding of the latter, recent work has utilized ChIP-seq (chromatin immunoprecipitation followed by sequencing) to reconstruct histone landscapes. This indicated that for dental pulp pericytes, the odontoblast-specific gene Dspp was found in a transcriptionally permissive state, while in bone marrow pericytes, the osteoblast-specific gene Runx2 was primed for expression. RNA sequencing has also been utilized to further characterize the 2 pericyte populations, and results highlighted that dental pulp pericytes are already precommitted to an odontoblast fate based on enrichment analysis indicating overrepresentation of key odontogenic genes. Furthermore, ChIP-seq analysis of the polycomb repressive complex 1 component RING1B indicated that this complex is likely to be involved in inhibiting inappropriate differentiation, as it localized to a number of loci of key transcription factors that are needed for the induction of adipogenesis, chondrogenesis, or myogenesis. In this review, we highlight recent data elucidating molecular mechanisms that indicate that pericytes can be tissue-specific precommitted MSC precursors in vivo and that this precommitment is a major driving force behind MSC differentiation.

Microvesicles enhance the mobility of human diabetic adipose tissue-derived mesenchymal stem cells in vitro and improve wound healing in vivo

2016 ◽  
Vol 473 (4) ◽  
pp. 1111-1118 ◽  
Author(s):  
Nhu Thuy Trinh ◽  
Toshiharu Yamashita ◽  
Tran Cam Tu ◽  
Toshiki Kato ◽  
Kinuko Ohneda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Improve Wound Healing

scholarly journals Recent Advances in Hydroxyapatite Scaffolds Containing Mesenchymal Stem Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
John Michel ◽  
Matthew Penna ◽  
Juan Kochen ◽  
Herman Cheung
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tissue Regeneration ◽  
Therapeutic Option ◽  
Synthetic Polymers ◽  
Review Article ◽  
Osteogenic Lineage ◽  
Wide Range

Modern day tissue engineering and cellular therapies have gravitated toward using stem cells with scaffolds as a dynamic modality to aid in differentiation and tissue regeneration. Mesenchymal stem cells (MSCs) are one of the most studied stem cells used in combination with scaffolds. These cells differentiate along the osteogenic lineage when seeded on hydroxyapatite containing scaffolds and can be used as a therapeutic option to regenerate various tissues. In recent years, the combination of hydroxyapatite and natural or synthetic polymers has been studied extensively. Due to the interest in these scaffolds, this review will cover the wide range of hydroxyapatite containing scaffolds used with MSCs forin vitroandin vivoexperiments. Further, in order to maintain a progressive scope of the field this review article will only focus on literature utilizing adult human derived MSCs (hMSCs) published in the last three years.

scholarly journals Hematopoietic stem cells can differentiate into pericytes and myofibroblast in wound healing, not bone Mesenchymal stem cells

2020 ◽  
Author(s):  
Yanan Kong ◽  
Liuhanghang Cheng ◽  
Min Xuan ◽  
Hao Ding ◽  
Biao Cheng
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Fluorescent Protein ◽  
Bone Mesenchymal Stem Cells ◽  
Hematopoietic Stem ◽  
Green Fluorescent

Abstract Background Hematopoietic stem cells(HSCs) and mesenchymal stem cells(MSCs) can participate in wound healing. However, very few studies had shown HSCs and MSCs could arrive to the wound and differentiate into tissues. In this study, we intend to investigate the role of bone marrow HSCs and MSCs in wound healing. Methods We first removed the bone marrow of mice by irradiation. Furthermore, we injected different colours of fluorescent HSCs and MSCs into the tail vein of irradiated mice to reconstruct bone marrow function. We prepared wound models on the back of these mice. In vivo imaging and immunohistochemical staining were used to track the expression of fluorescent protein. Results HSCs and MSCs have been isolated and cultured. HSCs expressed expressed Sca1, not lineage, CD34 or CD48. MSCs expressed expressed CD29 and CD44,not CD34 or CD45. HSCs labeled with green fluorescent protein reached the wound and co-expressed with desmin and α-SMA. MSCs didn’t stay on the wound. Conclusions The results show HSCs in the bone marrow of mice can directly participate in wound healing and differentiate into pericytes and myofibroblasts.

scholarly journals Dental-Derived Mesenchymal Stem Cells: State of the Art

2021 ◽  
Vol 9 ◽  
Author(s):  
Bo Li ◽  
Takehito Ouchi ◽  
Yubin Cao ◽  
Zhihe Zhao ◽  
Yi Men
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tissue Regeneration ◽  
Dental Pulp ◽  
State Of The Art ◽  
Neural Cells ◽  
Immune Microenvironment ◽  
Injury Repair ◽  
Apical Papilla ◽  
Mammalian Teeth

Mesenchymal stem cells (MSCs) could be identified in mammalian teeth. Currently, dental-derived MSCs (DMSCs) has become a collective term for all the MSCs isolated from dental pulp, periodontal ligament, dental follicle, apical papilla, and even gingiva. These DMSCs possess similar multipotent potential as bone marrow-derived MSCs, including differentiation into cells that have the characteristics of odontoblasts, cementoblasts, osteoblasts, chondrocytes, myocytes, epithelial cells, neural cells, hepatocytes, and adipocytes. Besides, DMSCs also have powerful immunomodulatory functions, which enable them to orchestrate the surrounding immune microenvironment. These properties enable DMSCs to have a promising approach in injury repair, tissue regeneration, and treatment of various diseases. This review outlines the most recent advances in DMSCs’ functions and applications and enlightens how these advances are paving the path for DMSC-based therapies.

scholarly journals Human bone marrow mesenchymal stem cells-derived exosomes stimulate cutaneous wound healing mediates through TGF-β/Smad signaling pathway

2020 ◽  
Author(s):  
Tiechao Jiang ◽  
Zhongyu Wang ◽  
Ji Sun
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Skin Cells ◽  
Smad Signaling Pathway ◽  
Marrow Mesenchymal Stem Cells

Abstract Background: Cutaneous wound healing represents a morphogenetic response to injury, and is designed to restore anatomic and physiological function. Human bone marrow mesenchymal stem cells-derived exosomes (hBM-MSCs-Ex) is a promising source for cell-free therapy and skin regeneration. Methods: In this study, we investigated the cell regeneration effects and its underlying mechanism of hBM-MSCs-Ex on cutaneous wound healing in rats. In vitro studies, we evaluated the role of hBM-MSCs-Ex in the two types of skin cells: human keratinocytes (HaCaT) and human dermal fibroblasts (HDFs) for the proliferation. For in vivo studies, we used a full-thickness skin wound model to evaluate the effects of hBM-MSCs-Ex on cutaneous wound healing in vivo. Results: The results demonstrated that hBM-MSCs-Ex promote both two types of skin cells growth effectively and accelerate the cutaneous wound healing. Interestingly, we found that hBM-MSCs-Ex significantly down-regulated TGF-β1, Smad2, Smad3, and Smad4 expression, while up-regulated TGF-β3 and Smad7 expression in the TGF-β/Smad signaling pathway. Conclusions: Our findings indicated that hBM-MSCs-Ex effectively promote the cutaneous wound healing through inhibiting the TGF-β/Smad signal pathway. The current results providing a new sight for the therapeutic strategy for the treatment of cutaneous wounds.

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