Biochemical and Biophysical Research Communications
Placenta mesenchymal stem cell accelerates wound healing by enhancing angiogenesis in diabetic Goto-Kakizaki (GK) rats
Introduction
Diabetes mellitus is increasing in incidence and represents a major health problem in the twenty-first century. Indeed, the total number of diabetic patients has been projected to increase from 171 million in 2000 to 366 million in 2030 [1]. Chronic skin ulcers are one of the most serious consequences of diabetes, representing a major contributing factor to amputation in diabetics [2]. The annual incidence of foot ulcers among diabetic patients has been variously estimated at between 1% and 4.1%, and the annual incidence of amputation is in the range 0.21% and 1.37% [3]. The economic and social costs associated with chronic wounds are enormous and include hospital costs, disability, decreased productivity and loss of independence. A number of factors have been implicated in the predisposition to non-healing wounds observed in diabetes, including microvascular disease, peripheral neuropathy and impaired angiogenesis of wounds [4]. Of these factors, angiogenesis is considered to play a pivotal pathophysiological role by virtue of its requirement in successful wound repair.
Human mesenchymal stem cells (MSCs)-based therapeutic angiogenesis has emerged as a promising strategy in regenerative medicine, including in the treatment of myocardial infarction [5], limb ischemia [6] and chronic skin ulcers [7], [8]. Particularly, bone marrow MSCs (BM-MSCs) [9] and endothelial progenitor cells (EPCs) [10] have been subjected to the most comprehensive translational and human studies of all stem cell approaches in wound healing. However, the use of BM-MSCs and EPCs is associated with some deficiencies. The survival and differentiation potential of BM-MSCs or progenitor cells obtained from aged patients or patients with age-related disorders are impaired, thus limiting their therapeutic efficiency [11], [12]. Furthermore, autologous delivery of BM-MSCs or EPCs is inevitably associated with a delay in treatment due to time required for cell collection, isolation and propagation of sufficient numbers for injection [13]. Therefore, there is emerging interest in the identification of alternative cell sources of MSCs.
In the present study, a population of multipotent stem cells was isolated from human term placenta, a temporary organ with fetal contributions that is discarded postpartum. These placenta mesenchymal stem cells (PMSCs) display typical mesenchymal characteristics such as great capacity for self-renewal while maintaining their multipotent differentiation potential and expression of common MSCs surface markers similar to those expressed by BM-MSCs. We hypothesized that PMSCs administration may restore wound healing in pathological conditions. Therefore, the effect of PMSCs transplantation on the wound healing rate in diabetic Goto-Kakizaki (GK) rats was evaluated. Furthermore, the mechanisms underlying the beneficial effects of PMSCs were assessed by analysis of their capacity of differentiation into endothelial cells and secretion of proangiogenic factors.
Section snippets
Patient selection and tissue processing
With consent, fresh placentas were collected from normal, full-term (38–40 weeks gestation), healthy donor mothers according to the regulations of the Independent Ethics Committee of the Shanghai Ninth People’s Hospital affiliated with Shanghai JiaoTong University School of Medicine. Written informed consent was signed prior to the study. Umbilical cord blood was allowed to drain from the placentas, which were then dissected carefully. All tissues were tested to exclude HIV-infection,
Characterization of PMSCs
We began our studies with the derivation and passaging of PMSCs as described under methods. To characterize the phenotypes of PMSCs, flow cytometry was performed to analyze surface markers of PMSCs. In this study, most of the PMSCs strongly expressed CD29, CD90, CD73, CD105 and CD49b but were negative for HLA-DR, CD45, and CD34. The immunophenotype of PMSCs remained unchanged for more than eight cell passages. PMSCs were also shown to give rise to adipogenic, chondrogenic and osteogenic
Discussion
The major goal of this study was to investigate the impact of transplanted PMSCs on the wound healing process in diabetic rats. To this end, our results demonstrate for the first time that PMSCs transplantation remarkably increased the wound healing rate and improved the condition of the scar by histological evaluation as well as by surface inspection. The greater potential of PMSCs may be related to the vascular differentiation capacity of these cells, as well as paracrine mechanisms. Local
Acknowledgments
This work was supported by the National Natural Science Foundation of China (Grant Nos. 81000345, 81200244) and by the Shanghai Natural Science Foundation (Grant Nos. 09ZR1417100 and 12ZR1428400). We thanks very much for the English editing by Medsci company.
References (34)
- et al.
Autologous bone-marrow stem-cell transplantation for myocardial regeneration
Lancet
(2003) - et al.
Bone marrow-derived endothelial progenitor cells do not contribute significantly to new vessels during incisional wound healing
Exp. Hematol.
(2007) - et al.
Treatment of myocardial ischemia with bone marrow-derived mesenchymal stem cells overexpressing hepatocyte growth factor
Mol. Ther.
(2003) - et al.
Platelet activation increases with the severity of peripheral arterial disease: implications for clinical management
J. Vasc. Surg.
(2007) - et al.
Cell therapy in critical limb ischemia: current developments and future progress
Cytotherapy
(2012) - et al.
Enhancement of differentiation efficiency of hESCs into vascular lineage cells in hypoxia via a paracrine mechanism
Stem Cell Res.
(2011) - et al.
Contribution of marrow-derived progenitors to vascular and cardiac regeneration
Semin. Cell Dev. Biol.
(2002) - et al.
Angiogenesis in ischemic tissue produced by spheroid grafting of human adipose-derived stromal cells
Biomaterials
(2011) - et al.
Paracrine effects of mesenchymal stem cells enhance vascular regeneration in ischemic murine skin
Microvasc. Res.
(2012) - et al.
Endothelial progenitor cells for postnatal vasculogenesis
Am. J. Physiol. Cell Physiol.
(2004)
Hyperoxia, endothelial progenitor cell mobilization, and diabetic wound healing
Antioxid. Redox Signal.
Reducing the incidence of foot ulceration and amputation in diabetes
Curr. Diab. Rep.
Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings
Diab. Care
Both cultured and freshly isolated adipose tissue-derived stem cells enhance cardiac function after acute myocardial infarction
Eur. Heart J.
In vivo functional and transcriptional profiling of bone marrow stem cells after transplantation into ischemic myocardium
Arterioscler. Thromb. Vasc. Biol.
Human adipose-derived stromal cells accelerate diabetic wound healing: impact of cell formulation and delivery
Tissue Eng. Part A
Concise review: bone marrow-derived stem/progenitor cells in cutaneous repair and regeneration
Stem Cells
Cited by (118)
Bioactive functional scaffolds for stem cells delivery in wound healing and skin regeneration
2022, Reactive and Functional PolymersThe remarkable effect of menstrual blood stem cells seeded on bilayer scaffold composed of amniotic membrane and silk fibroin aiming to promote wound healing in diabetic mice
2022, International ImmunopharmacologyCitation Excerpt :Among recruited stem cells, mesenchymal stem cells (MSCs) are reliable type of adult stem cells that can be isolated from a different variety of sources, such as bone marrow, adipose tissue, and umbilical cord blood. Although, MSCs display regenerative and immunomodulatory properties in wound healing [20–25], some limitations have been attributed to MSCs recruitment include no enough availability and accessibility, ethical concerns, and invasive procedures required for sample collection [26]. As we proposed earlier [14], menstrual blood-derived mesenchymal stem cells (MenSCs) with advantages including availability, easy accessibility and promising therapeutic properties especially immunomodulatory, angiogenic, and migratory capacities in combination with a bilayer amniotic membrane/nano-fibrous silk fibroin scaffold could accomplish effective regenerative functions in chronic wound healing.
Improved wound healing of diabetic foot ulcers using human placenta-derived mesenchymal stem cells in gelatin electrospun nanofibrous scaffolds plus a platelet-rich plasma gel: A randomized clinical trial
2021, International ImmunopharmacologyCitation Excerpt :They display low immunogenicity and have beneficial biological effects such as anti-inflammatory, antimicrobial, anti-fibrosis and anti-scarring properties [28]. During the early inflammatory stage of wound healing, PDMSCs can inhibit the proinflammatory response, and increase the expression of the anti-inflammatory factor IL-10, along with growth factors, cytokines and chemokines, which have a positive effect on wound repair [10,12]. Promotion of epithelization [29] and in vivo antimicrobial activity [30,31] are other properties of PDMSCs.
- 1
Poren Kong (Chinese name: Boren Jiang) and Xiaoyun Xie contributed equally to this work.