Concise Review: Mesenchymal Stem Cells and Translational Medicine: Emerging Issues

Ren, Guangwen; Chen, Xiao; Dong, Fengqin; Li, W; Ren, Xiaohui; Zhang, Yanyun; Shi, Yufang

doi:10.5966/sctm.2011-0019

Cited by 295 publications

(262 citation statements)

References 107 publications

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“…Preliminary investigations have been carried out in different autoimmune diseases like multiple sclerosis, Crohn's disease, systemic lupus, type 1 diabetes mellitus, systemic vasculitides, SSc, and in graft-versushost disease (39,42). In addition, because of their potential angiogenic effects, MSCs have been proposed to be useful in the treatment of various vascular ischemic conditions (31).…”

Section: Discussionmentioning

confidence: 99%

Autologous Fat Grafting in the Treatment of Fibrotic Perioral Changes in Patients with Systemic Sclerosis

et al. 2015

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Autologous fat tissue grafting (AFTG) has been successfully used in the treatment of different sclerotic conditions, including localized scleroderma. Patients with advanced systemic sclerosis (SSc)-related perioral thickening and mouth opening limitation are candidates for this therapeutic approach. AFTG of the lips was performed to improve mouth opening in patients with SSc. We enrolled in the study 20 female patients with diffuse SSc (median age 35 ± 15 years and 11 ± 10 years of disease duration). Two-milliliter fractions of autologous fat drawn from trochanteric or periumbilical areas were injected in eight different sites around the mouth. Baseline and after-treatment mouth opening changes were assessed by measuring interincisal distance and oral perimeter, while skin hardness was tested by digital durometer. Pre-and posttreatment modifications of microvascular architecture were assessed by counting capillaries in the inferior lip videocapillaroscopy (VC) images and by scoring the microvascular density (MVD) in anti-CD34/CD31 immunohistochemical (IH) stained perioral skin biopsy sections. Similarly, histological sections were examined to evaluate dermoepidermic junction (DEJ) modifications. Three months after treatment, both the interincisal distance and oral perimeter significantly increased (p < 0.001). At the same time, a significant skin neovascularization became evident, both considering the VC images (p < 0.001) and MVD scores in IH sections (p < 0.0001). Finally, some skin histological aspects also improved, as shown by the significant changes in DEJ flattening scores (p < 0.0001). The present study suggests that, in patients with SSc, AFTG can improve mouth opening and function, induce a neovascularization, and partially restore the skin structure.

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Section: Discussionmentioning

confidence: 99%

Autologous Fat Grafting in the Treatment of Fibrotic Perioral Changes in Patients with Systemic Sclerosis

et al. 2015

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“…2,3 MSCs are non-hematopoietic spindle-shaped fibroblast-like cells derived from the mesoderm. 4 MSCs possess self-renewal and immunomodulatory properties, are capable of transdifferentiation, and participate in wound healing, bone regeneration, angiogenesis, and homeostasis. [5][6][7] Due to these characteristics, MSCs therefore, tumors are sometimes called wounds that do not heal.…”

Section: Introductionmentioning

confidence: 99%

Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors

Dapkutė¹,

Steponkienė²,

Bulotienė³

et al. 2017

IJN

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Purpose Cell-mediated delivery of nanoparticles is emerging as a new method of cancer diagnostics and treatment. Due to their inherent regenerative properties, adult mesenchymal stem cells (MSCs) are naturally attracted to wounds and sites of inflammation, as well as tumors. Such characteristics enable MSCs to be used in cellular hitchhiking of nanoparticles. In this study, MSCs extracted from the skin connective tissue were investigated as transporters of semiconductor nanocrystals quantum dots (QDs). Materials and methods Cytotoxicity of carboxylated CdSe/ZnS QDs was assessed by lactate dehydrogenase cell viability assay. Quantitative uptake of QDs was determined by flow cytometry; their intracellular localization was evaluated by confocal microscopy. In vitro tumor-tropic migration of skin-derived MSCs was verified by Transwell migration assay. For in vivo migration studies of QD-loaded MSCs, human breast tumor-bearing immunodeficient mice were used. Results QDs were found to be nontoxic to MSCs in concentrations no more than 16 nM. The uptake studies showed a rapid QD endocytosis followed by saturating effects after 6 h of incubation and intracellular localization in the perinuclear region. In vitro migration of MSCs toward MDA-MB-231 breast cancer cells and their conditioned medium was up to nine times greater than the migration toward noncancerous breast epithelial cells MCF-10A. In vivo, systemically administered QD-labeled MSCs were mainly located in the tumor and metastatic tissues, evading most healthy organs with the exception being blood clearance organs (spleen, kidneys, liver). Conclusion Skin-derived MSCs demonstrate applicability in cell-mediated delivery of nanoparticles. The findings presented in this study promise further development of a cell therapy and nanotechnology-based tool for early cancer diagnostics and therapy.

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“…The therapeutic potential of transfused MSCs has been demonstrated in animal models of experimental autoimmune encephalitis, diabetes, rheumatoid arthritis, myocardial infarction, acute lung injury, retinal degeneration, acute renal failure, and transplant rejection (9,10). In human phase II clinical trials, MSCs were shown to be effective in treating graft-versus-host disease (11), although study of an industrial MSC product in a phase III trial was negative (12)(13)(14).…”

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confidence: 99%

IDO-Independent Suppression of T Cell Effector Function by IFN-γ–Licensed Human Mesenchymal Stromal Cells

Chinnadurai

Copland

Patel

et al. 2014

The Journal of Immunology

227

214

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Human bone marrow–derived mesenchymal stromal cells (MSCs) inhibit proliferation of activated T cells, and IFN-γ plays an important role in this process. This IFN-γ–licensed veto property is IDO-dependent. To further decipher the mechanistic underpinnings of MSC veto function on T cells, we investigated the effect of MSCs and IFN-γ–licensed MSCs on T cell effector function as assayed by cytokine secretion of T cells. Although MSCs and IFN-γ–licensed MSCs inhibit T cell proliferation, only IFN-γ–licensed MSCs significantly inhibit Th1 cytokine (IFN-γ, TNF-α, and IL-2) production by T cells. Additionally, IFN-γ–licensed MSCs inhibit T cell degranulation as well as single, double, and triple cytokine–producing T cells. Although IFN-γ–licensed MSCs upregulate their IDO activity, we found that MSC IDO catalytic function is dispensable with regard to MSC-driven inhibition of T cell effector function. Novel flow cytometry based functional screening of MSC-expressed, IFN-γ–licensed inhibitory molecules identified B7H1 and B7DC/PD1 pathways as essential effectors in blocking T cell function. Small interfering RNA–mediated blocking of B7H1 and B7DC reverses the inhibitory potential of IFN-γ–licensed MSCs on T cell effector function. Mechanistic analysis revealed that clustering of MHC and coinhibitory molecules are indispensable for the inhibitory effect of IFN-γ MSCs. Although exogenous IL-2 reverses B7H1-Ig–mediated inhibition of T cell proliferation, it does not affect the veto function of IFN-γ MSCs on both T cell proliferation and effector function. Our results reveal a new immunosuppressive property of IFN-γ–licensed MSCs that inhibits T cell effector function independent of IDO but through the ligands for PD1.

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Concise Review: Mesenchymal Stem Cells and Translational Medicine: Emerging Issues

Abstract: ABSTRACT

Cited by 295 publications

References 107 publications

Autologous Fat Grafting in the Treatment of Fibrotic Perioral Changes in Patients with Systemic Sclerosis

Autologous Fat Grafting in the Treatment of Fibrotic Perioral Changes in Patients with Systemic Sclerosis

Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors

IDO-Independent Suppression of T Cell Effector Function by IFN-γ–Licensed Human Mesenchymal Stromal Cells

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