Improvement Of Angiogenesis Research Articles

In-vitro and in-vivo evaluation of angiogenic potential of a novel lithium chloride loaded silk fibroin / alginate 3D porous scaffold with antibacterial activity, for promoting diabetic wound healing

Healing diabetic ulcers with chronic inflammation is a major challenge for researchers and professionals, necessitating new strategies. To rapidly treat diabetic wounds in rat models, we have fabricated a composite scaffold composed of alginate (Alg) and silk fibroin (SF) as a wound dressing that is laden with molecules of lithium chloride (LC). The physicochemical, bioactivity, and biocompatibility properties of Alg-SF-LC scaffolds were investigated in contrast to those of Alg, SF, and Alg-SF ones. Afterward, full-thickness wounds were ulcerated in diabetic rats in order to evaluate the capacity of LC-laden scaffolds to regenerate skin. The characterization findings demonstrated that the composite scaffolds possessed favorable antibacterial properties, cell compatibility, high swelling, controlled degradability, and good uniformity in the interconnected pore microstructure. Additionally, in terms of wound contraction, re-epithelialization, and angiogenesis improvement, LC-laden scaffolds revealed better performance in diabetic wound healing than the other groups. This research indicates that utilizing lithium chloride molecules loaded in biological materials supports the best diabetic ulcer regeneration in vivo, and produces a skin replacement with a cellular structure comparable to native skin.

Correction: Left Ventricular Geometry and Angiogenesis Improvement in Rat Chronic Ischemic Cardiomyopathy following Injection of Encapsulated Mesenchymal Stem Cells.

In this article published in Cell J, Vol 24, No 12, 2022, on pages 741-747, the authors found that there was some mistakes in the Table 1 and we have corrected them in the following table. The authors would like to apologize for any inconvenience.

A self-powered, anti-bacterial, moist-wound dressing made with electroactive free-flowing hydrogel particles, encourage faster wound closure

Chronic exuding wounds continue to present a significant healthcare challenge, with prolonged healing times and an increased risk of complications. The wounds with their complex contours and hard-to-reach areas, can particularly benefit from the advantages offered by free-flowing hydrogel particles. Innovative approaches are needed to enhance the healing process and improve outcomes in wound care. Building upon previous research on piezo-driven electrical stimulation, herein, we introduce self-powered, silver nanoparticles containing electroactive hydrogel particles as an innovative wound dressing specifically designed to fill deep irregular wound cavities. Apart from providing anti-bacterial and a moist wound environment, the hydrogel particles provide electrical stimulation to the wound-bed. The self-powered dressing eliminates the need for an external power source by harnessing the electrical activity from a piezo-responsive polyvinylidene fluoride (PVDF) membrane, thereby improving patient compliance. The electroactive hydrogel particles exhibited improved cellular responses including cell migration, proliferation and angiogenesis. Accelerated wound closure, increase in collagen synthesis and improvement in angiogenesis was observed in rats treated with the dressing. By elucidating the mechanisms and benefits of this innovative approach, we seek to highlight its potential as an effective and practical solution for the treatment of challenging wounds.

Targeted modulation of intestinal epithelial regeneration and immune response in ulcerative colitis using dual-targeting bilirubin nanoparticles.

Rationale: The therapeutic benefits of bilirubin in the treatment of ulcerative colitis (UC) are considerable, whereas the underlying mechanism of bilirubin on UC remains unclear remains unexplored. In addition, the weak hydrophilicity and toxicity have limited its translational applications. Methods: We have developed a colon dual-targeting nanoparticle, for orally delivering bilirubin through hydrogel encapsulation of hyaluronic acid (HA)-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles (HA-PLGABilirubin). Confocal microscopy and in vivo imaging were used to evaluate the uptake and the targeted property of HA-PLGABilirubin in UC. Immunohistochemistry, immunofluorescence, and transcriptomic analyses were applied to examine the therapeutic effect and potential mechanism of HA-PLGABilirubin in UC. Results: Our results indicated that HA-PLGAbilirubin can significantly enhance the release of bilirubin at simulated intestinal pH and demonstrate higher cellular uptake in inflammatory macrophages. Moreover, in vivo biodistribution studies revealed high uptake and retention of HA-PLGAbilirubin in inflamed colon tissue of UC mouse model, resulting in effective recovery of intestinal morphology and barrier function. Importantly, HA-PLGAbilirubin exerted potent therapeutic efficacy against ulcerative colitis through modulating the intestinal epithelial/stem cells regeneration, and the improvement of angiogenesis and inflammation. Furthermore, genome-wide RNA-seq analysis revealed transcriptional reprogramming of immune response genes in colon tissue upon HA-PLGAbilirubin treatment in UC mouse model. Conclusion: Overall, our work provides an efficient colon targeted drug delivery system to potentiate the treatment of ulcerative colitis via modulating intestinal epithelium regeneration and immune response in ulcerative colitis.

Extracellular Vesicles from NMN Preconditioned Mesenchymal Stem Cells Ameliorated Myocardial Infarction via miR-210-3p Promoted Angiogenesis

Mesenchymal stem cell-derived extracellular vesicles (MSCs-EVs) possess cardioprotection in acute myocardial infarction. Nevertheless, the therapeutic intervention potential and the molecular mechanism of EVs from NMN (Nicotinamide mononucleotide) preconditioned hUCMSCs (N-EVs) in acute myocardial infarction remains unknown. In the present study, EVs from hUCMSCs (M-EVs) and N-EVs were identified by electron microscopy, immunoblotting and nanoparticle tracking analysis. Compared with M-EVs, N-EVs significantly increased the proliferation, migration, and angiogenesis of HUVECs. Meanwhile, N-EVs markedly reduced apoptosis and cardiac fibrosis and promoted angiogenesis in the peri-infarct region in the MI rats. A high-throughput miRNA sequencing and qPCR methods analysis revealed that miR-210-3p was abundant in N-EVs and the expression of miR-210-3p was obviously upregulated in HUVECs after N-EVs treated. Overexpression of miR-210-3p in HUVECs significantly enhanced the tube formation, migration and proliferative capacities of HUVECs. However, downregulation of miR-210-3p in HUVECs markedly decreased the tube formation, migration and proliferative capacities of HUVECs. Furthermore, bioinformatics analysis and luciferase assays revealed that EphrinA3 (EFNA3) was a direct target of miR-210-3p. Knockdown of miR-210-3p in N-EVs significantly impaired its ability to protect the heart after myocardial infarction. Altogether, these results indicated that N-EVs promoted the infarct healing through improvement of angiogenesis by miR-210-3p via targeting the EFNA3. Graphical Created with Biorender.com.

In Situ Biomimetic Mineralization of Bone-Like Hydroxyapatite in Hydrogel for the Acceleration of Bone Regeneration

A critical-sized bone defect, which cannot be repaired through self-healing, is a major challenge in clinical therapeutics. The combination of biomimetic hydrogels and nano-hydroxyapatite (nano-HAP) is a promising way to solve this problem by constructing an osteogenic microenvironment. However, it is challenging to generate nano-HAP with a similar morphology and structure to that of natural bone, which limits the improvement of bone regeneration hydrogels. Inspired by our previous works on organic-inorganic cocross-linking, here, we built a strong organic-inorganic interaction by cross-linking periosteum-decellularized extracellular matrix and calcium phosphate oligomers, which ensured the in situ mineralization of bone-like nano-HAP in hydrogels. The resulting biomimetic osteogenic hydrogel (BOH) promotes bone mineralization, construction of immune microenvironment, and angiogenesis improvement in vitro. The BOH exhibited acceleration of osteogenesis in vivo, achieving large-sized bone defect regeneration and remodeling within 8 weeks, which is superior to many previously reported hydrogels. This study demonstrates the important role of bone-like nano-HAP in osteogenesis, which deepens the understanding of the design of biomaterials for hard tissue repair. The in situ mineralization of bone-like nano-HAP emphasizes the advantages of inorganic ionic oligomers in the construction of organic-inorganic interaction, which provides an alternative method for the preparation of advanced biomimetic materials.

Left Ventricular Geometry and Angiogenesis Improvement in Rat Chronic Ischemic Cardiomyopathy following Injection of Encapsulated Mesenchymal Stem Cells.

Injection of hydrogel and cells into myocardial infarction (MI) patients is one of the emerging treatment techniques, however, it has some limitations such as a lack of electromechanical properties and neovascularization. We investigated the therapeutic potential of new electroactive hydrogel [reduced graphene oxide (rGO)/Alginate (ALG)] encapsulated human bone marrow mesenchymal stem cells (BMSCs). The experimental study involved ligating the left anterior descending coronary artery (LAD) in rat models of chronic ischemic cardiomyopathy. Echocardiograms were analyzed at 4 and 8 weeks after MI treatment. In the eighth week after injection in the heart, the rats were sacrificed. Histological and immunohistochemical analyses were performed using Hematoxylin and Eosin (H and E) staining, Masson's trichrome staining and anti-CD31 antibody to analyze tissue structure and detect neovascularization. In comparison to the control and other treatment groups, MSCs encapsulated in rGO-ALG showed significant improvements in fractional shortening (FS), ejection fraction (EF), wall thickness and internal diameters (P<0.05). The morphological observation showed several small blood vessels formed around the transplantation site in all treated groups especially in the MSC-ALG-rGO group 8 weeks after the transplantation. Also, Masson's trichrome staining indicated an increased amount of collagen fibers in rGO-ALG-MSC. Microvessel density was significantly higher using MSC-ALG-rGO compared to controls (P<0.01). This study demonstrates that intramyocardial injection of rGO/ALG, a bio-electroactive hydrogel, is safe for increasing LV function, neovascularization, and adjusting electrical characteristics following MI. The results confirm ALG promising capability as a natural therapeutic for cardiac regeneration.

Roles of MicroRNA-21 in Skin Wound Healing: A Comprehensive Review.

MicroRNA-21 (miR-21), one of the early mammalian miRNAs identified, has been detected to be upregulated in multiple biological processes. Increasing evidence has demonstrated the potential values of miR-21 in cutaneous damage and skin wound healing, but lack of a review article to summarize the current evidence on this issue. Based on this review, relevant studies demonstrated that miR-21 played an essential role in wound healing by constituting a complex network with its targeted genes (i.e., PTEN, RECK. SPRY1/2, NF-κB, and TIMP3) and the cascaded signaling pathways (i.e., MAPK/ERK, PI3K/Akt, Wnt/β-catenin/MMP-7, and TGF-β/Smad7-Smad2/3). The treatment effectiveness developed by miR-21 might be associated with the promotion of the fibroblast differentiation, the improvement of angiogenesis, anti-inflammatory, enhancement of the collagen synthesis, and the re-epithelialization of the wound. Currently, miRNA nanocarrier systems have been developed, supporting the feasibility clinical feasibility of such miR-21-based therapy. After further investigations, miR-21 may serve as a potential therapeutic target for wound healing.

PlGF Reduction Compromises Angiogenesis in Diabetic Foot Disease Through Macrophages.

Diabetic foot disease (DFD) is a common and serious complication for diabetes and is characterized with impaired angiogenesis. In addition to the well-defined role of vascular endothelial growth factor (VEGF) -A and its defect in the pathogenesis of DFD, another VEGF family member, placental growth factor (PlGF), was also recently found to alter expression pattern in the DFD patients with undetermined mechanisms. This question was thus addressed in the current study. We detected attenuated PlGF upregulation in a mouse DFD model. In addition, the major cell types at the wound to express the unique PlGF receptor, VEGF receptor 1 (VEGFR1), were macrophages and endothelial cells. To assess how PlGF regulates DFD-associated angiogenesis, we injected recombinant PlGF and depleted VEGF1R specifically in macrophages by local injection of an adeno-associated virus (AAV) carrying siRNA for VEGFR1 under a macrophage-specific CD68 promoter. We found that the angiogenesis and recovery of the DFD were both improved by PlGF injection. The PlGF-induced improvement in angiogenesis and the recovery of skin injury were largely attenuated by macrophage-specific depletion of VEGF1R, likely resulting from reduced macrophage number and reduced M2 polarization. Together, our data suggest that reduced PlGF compromises angiogenesis in DFD at least partially through macrophages.

Modulation of macrophages by a paeoniflorin-loaded hyaluronic acid-based hydrogel promotes diabetic wound healing.

The impaired wound healing in diabetes is a central concern of healthcare worldwide. However, current treatments often fail due to the complexity of diabetic wounds, and thus, emerging therapeutic approaches are needed. Macrophages, a prominent immune cell in the wound, play key roles in tissue repair and regeneration. Recent evidence has demonstrated that macrophages in diabetic wounds maintain a persistent proinflammatory phenotype that causes the failure of healing. Therefore, modulation of macrophages provides great promise for wound healing in diabetic patients. In this study, the potential of paeoniflorin (PF, a chemical compound derived from the herb Paeonia lactiflora) for the transition of macrophages from M1 (proinflammatory phenotype) to M2 (anti-inflammatory/prohealing phenotype) was confirmed using ex vivo and in vivo experimental approaches. A hydrogel based on high molecular weight hyaluronic acid (HA) was developed for local administration of PF in experimental diabetic mice with a full-thickness wound. The resultant formulation (HA-PF) was able to significantly promote cutaneous healing as compared to INTRASITE Gel (a commercial hydrogel wound dressing). This outcome was accompanied by the amelioration of inflammation, the improvement of angiogenesis, and re-epithelialization, and the deposition of collagen. Our study indicates the significant potential of HA-PF for clinical translation in diabetic wound healing.

Comparative efficacy оf non-surgical correction of early-onset genital prolapse based on differentiated approach

The paper presents the results of the comparative efficacy of non-surgical correction of early-onset genital prolapse (GP) in women of perimenopausal and menopausal age using differentiated approach. The objective: to study morphological traits of the vaginal walls and to compare the effectiveness of non-surgical techniques of GP correction. Materials and methods. The study involved 120 patients with early-onset GP. The treatment group (Group 1) consisted of 90 women with GP who were divided into three subgroups depending on the non-surgical correction technique chosen (utility model patent No.145380 from 10.12.2020): 1a (n=30) – GP correction by platelet-rich autoplasma, 1b (n=30) – GP correction by hyaluronic acid-based agent, 1c (n=30) GP correction using СО2 laser radiation. The experimental group (Group 2) consisted of 30 patients who underwent GP correction by training the pelvic floor muscles individually according to the standard method.Results. Three months after the treatment according to the patented method, the number of patients with GP of grade 2 decreased by 16.7% in group 1a, by 31.3% in group 1b and by 41.2% in group 1c. In patients of 1c subgroup, where the presence of the combined type (cystorectocele) of GP prevailed, in 19 women (63.3%) after the treatment there was an improvement in the morphological structure of the vaginal wall, which was manifested by a pronounced diffuse improvement in angiogenesis (in all layers) due to neoangiogenesis, preserved structure of collagen fibers with increasing density of the latter in the absence of signs of edema and mild degenerative changes. It should be noted that in subgroup 1b, three months after the treatment 17 (56.6%) women had no complaints which was associated with a significant improvement in the indicator of the size of elastin and collagen fibers, and only in 9 patients (30%) this indicator remained without changes. In subgroup 1a, the evaluation of the effectiveness of the non-surgical technique showed that only 10 (33.3%) women had a slight improvement in quality of life compared to baseline before treatment. In the experimental group, there was no positive dynamics, and in 9 women (30%) three months after the treatment there was an increase in manifestations of GP and symptoms associated with it, which was confirmed by such morphological changes as minimal focal signs of neoangiogenesis, thinned, significantly swollen collagen fibers, surrounded by interlayers of connective tissue.Conclusions. This algorithmic approach in non-surgical correction of GP contributes not only to the effective treatment of early-onset GP, prevention of further progression, but also to a significant improvement in quality of life.

Comparative Dose of Intracarotid Autologous Bone Marrow Mononuclear Therapy in Chronic Ischemic Stroke in Rats

Research on chronic ischemic stroke is limited. One of the more promising approaches showing positive effects in the acute stage is mononuclear bone marrow cell therapy. This research may be the first which presents data about the optimum dose of bone marrow mononuclear cells (BM-MNCs) for chronic ischemic stroke in rats and discusses factors influencing recovery in the chronic stage.&#x0D; We performed temporary middle cerebral artery occlusion (MCAO) procedures on the rats which were then randomly assigned to one of two experimental groups in which they were given either low or high doses of autologous BM-MNCs (5 million or 10 million cells per kg body weight). &#x0D; Rat brains were fixed for HE, CD31, and doublecortin staining for analysis of the effects. Rat behavior was assessed weekly using the cylinder test and a modified neurological severity score (NSS) test. &#x0D; In the four weeks prior to administration of BM-MNC, cylinder test scores improved to near normal, and NSS test scores improved moderately. The infarct zone decreased significantly (p &lt;0,01), there was an improvement in angiogenesis (p = 0.1590) and a significant improvement in neurogenesis (p &lt;0,01). Reduction of the infarct zone was associated with a higher dose whereas both higher and lower doses were found to have a similar effect on improving angiogenesis, and neurogenesis. Recovery was superior after twelve weeks compared with the recovery assessment at eight weeks. &#x0D; In conclusion, a dose of 10 million cells was more effective than a dose of 5 million cells per kg body weight for reducing the infarct zone and ameliorating neurogenesis. There was an improvement of histopathological parameters associated with the longer infarct period.

Улучшение процессов ангиогенеза и репродуктивных исходов у пациенток с хроническим эндометритом

Улучшение процессов ангиогенеза и репродуктивных исходов у пациенток с хроническим эндометритом

Neurotrophin-3 contributes to benefits of human embryonic stem cell-derived cardiovascular progenitor cells against reperfused myocardial infarction.

Acute myocardial infarction (MI) resulting from coronary ischemia is a major cause of disability and death worldwide. Transplantation of human embryonic stem cell (hESC)‐derived cardiovascular progenitor cells (hCVPCs) promotes the healing of infarcted hearts by secreted factors. However, the hCVPC‐secreted proteins contributing to cardiac repair remain largely unidentified. In this study, we investigated protective effects of neurotrophin (NT)‐3 secreted from hCVPCs in hearts against myocardial ischemia/reperfusion (I/R) injury and explored the underlying mechanisms to determine the potential of using hCVPC products as a new therapeutic strategy. The implantation of hCVPCs into infarcted myocardium at the beginning of reperfusion following 1 hour of ischemia improved cardiac function and scar formation of mouse hearts. These beneficial effects were concomitant with reduced cardiomyocyte death and increased angiogenesis. Moreover, hCVPCs secreted a rich abundance of NT‐3. The cardioreparative effect of hCVPCs in the I/R hearts was mimicked by human recombinant NT‐3 (hNT‐3) but canceled by NT‐3 neutralizing antibody (NT‐3‐Ab). Furthermore, endogenous NT‐3 was detected in mouse adult cardiomyocytes and its level was enhanced in I/R hearts. Adenovirus‐mediated NT‐3 knockdown exacerbated myocardial I/R injury. Mechanistically, hNT‐3 and endogenous NT‐3 inhibited I/R‐induced cardiomyocyte apoptosis through activating the extracellular signal‐regulated kinase (ERK) and reducing the Bim level, resulting in the cardioreparative effects of infarcted hearts together with their effects in the improvement of angiogenesis. These results demonstrate for the first time that NT‐3 is a cardioprotective factor secreted by hCVPCs and exists in adult cardiomyocytes that reduces I/R‐induced cardiomyocyte apoptosis via the ERK‐Bim signaling pathway and promotes angiogenesis. As a cell product, NT‐3 may represent as a noncell approach for the treatment of myocardial I/R injury.

Oral Administration of Aloe vera Ameliorates Wound Healing through Improved Angiogenesis and chemotaxis in Sprague Dawley Rats.

Aloe vera has been reported as a topical antibiotic and healing agent for wounds, but advantages of oral administration and mechanisms of wound healing have not been reported. Present study focuses on the evaluation of effects of oral administration of Aloe vera for excisional cutaneous wounds in Sprague Dawley rats. Sprague Dawley (SD) rats were inflicted with excisional wounds and were either treated with Aloe vera orally (Aloe vera) or kept untreated (wound). In contrast, healthy rats were kept as control group. Wound area was measured from day 7th to day 21st. Collagen content was estimated by hydroxyproline assay. Histology was analysed by hematoxylin and eosin staining. Angiogenesis was observed by indirect ELISA for Insulin like Growth Factor (IGF-1) and Vascular Endothelial Growth Factor (VEGF) protein from skin, serum and bone marrow. Chemotaxis was evaluated by RT-PCR analysis for Stromal cell-Derived Factor-1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR-4) from skin and bone marrow. Aloe vera healed wounds earlier than untreated rats with gradual improvement in wound areas and collagen content. Aloe vera also improved the expression of IGF-1 and VEGF in skin and bone marrow indicating an improvement in angiogenesis. RT- PCR analysis showed increased expression of genes for chemotaxis (SDF-1 and CXCR-4) in skin and bone marrow. Aloe vera improves healing by increasing collagen content, improving angiogenesis and chemotaxis.

Effective dosage of growth differentiation factor-9β in folliculogenesis and angiogenesis in the sheep ovarian tissues grafted onto chick embryo chorioallantoic membrane.

Scientists have tried to culture and transplant the ovarian tissues (OT), to preserve fertility in cancer patients. However, one of the main limitations to the applicability of this technique is the folliculogenesis disruption after transplantation. Due to the roles exerted by growth differentiation factor-9β (GDF9β), we decided to determine the most effective dose of GDF9β on promotion of folliculogenesis and angiogenesis in sheep OT grafted onto the chick chorioallantoic membrane (CAM). Fresh sheep OT were grafted onto the CAM for 5 days, and divided into four groups based on the addition of increasing doses of GDF9β (0, 150, 200 and 250 ng/mL). Following culture, histological (hematoxylin and eosin [H&E] staining) and immunohistological studies (Ki-67) were done. Fibrotic and necrotic regions were measured using MICROVISIBLE software. For comparing the follicle development rates between the groups as well as differences in the Ki-67-positive follicles, analysis of variance was applied. In both 200 and 250 ng/mL GDF9β groups, significantly higher rates of intermediary and primary follicles were observed, also the numbers of good quality follicles increased in the aforementioned groups and the rates of fibrotic and necrotic areas decreased. Moreover, in the 200 and 250 ng/mL GDF9β groups, the number of capillaries and the proliferative activity increased. The lower dose of GDF9β (150 ng/mL) neither activated the primordial follicles nor lead to an increase in the number of growing follicles. Addition of high dosages of GDF9β to the OT, grafted onto the CAM resulted in higher folliculogenesis and better transplantation features due to improvement in angiogenesis.

GelMA combined with sustained release of HUVECs derived exosomes for promoting cutaneous wound healing and facilitating skin regeneration.

It remains a clinical challenge for cutaneous wound healing and skin regeneration. Endothelial cells participate in the formation of blood vessels and play an important role in the whole process of wound healing. Recent studies suggested that exosomes contribute to the intercellular communication through paracrine pathways, and sustained release of exosomes from hydrogel-based materials provide a promising strategy for curing wound defects. In this study, we isolated exosomes derived from human umbilical vein endothelial cells (HUVECs) and found that HUVECs derived exosomes (HUVECs-Exos) could promote the proliferation and migration activities of keratinocytes and fibroblasts, which are two important effector cells for skin regeneration. Then we developed gelatin methacryloyl (GelMA) hydrogel as the wound dressing to incorporate HUVECs-Exos and applied it to the full-thickness cutaneous wounds. It demonstrated that GelMA scaffold could not only repair the wound defect, but also achieve sustained release of exosomes. The in vivo results showed accelerated re-epithelialization, promotion of collagen maturity and improvement of angiogenesis. Collectively, our findings suggested that HUVECs-Exos could accelerate wound healing and GelMA mediated controlled release of HUVECs-Exos might offer a new method for repairing cutaneous wound defects.

Mesenchymal stem cells improve survival in ischemic diabetic random skin flap via increased angiogenesis and VEGF expression.

Random skin flaps (RSFs) are cutaneous flaps. Despite the negative impact of diabetes mellitus (DM) on RSF viability, they are commonly used in diabetic patients. In this study, we have assessed bone marrow mesenchymal stem cell (BMMSC) treatment on RSF survival, tensiometrical parameters, angiogenesis, and mast cells (MCs) count in an ischemic RSF model in rats with type 1 DM (T1DM). We induced T1DM in 30 Wistar adult male rats. The animals were assigned to three groups of 10 rats per group as follows: group 1 (control); group 2 (placebo), and group 3 (BMMSCs). A 30 × 80 mm RSF was created in each rat. On day 7, we measured the viable portion of each RSF. A sample was taken for histological and immunohistochemistry studies, fibroblasts, MCs, angiogenesis, collagen bundle density, and the presence of vascular endothelial growth factor (VEGF)+ cells. An additional sample was taken to evaluate the flap's incision strength. Treatment with BMMSCs (17.8 ± 0.37) significantly increased RSF survival compared with the control (13.3 ± 0.35) and placebo (16.1 ± 0.27) groups (one-way analysis of variance, P = .000; least significant difference, P = .000, P = .002). There was a significant improvement in angiogenesis, as confirmed by stereologic examination. Assessment of VEGF+ cells showed prominent neovascularization in BMMSC-treated RSFs compared with the control and placebo groups. Subdermal injection of BMMSC significantly increased ischemic RSF survival as a result of stimulated neovascularization in T1DM rats. Treatment of diabetic RSF with BMMSCs showed no beneficial effects in the fibroblast number and biomechanical parameters for the repair of ischemic wounds in the rat model. Treatment with BMMSCs significantly increased collagen bundle density.

Sitagliptin protects diabetic rats with acute myocardial infarction through induction of angiogenesis: role of IGF-1 and VEGF.

Angiogenesis is regulated in a tissue-specific manner in all patients, especially those with diabetes. In this study, we describe a novel molecular pathway of angiogenesis regulation in diabetic rats with myocardial infarction (MI) and examine the cardioprotective effects of different doses of sitagliptin. Male rats were divided into 5 groups: normal vehicle group, diabetic group, diabetic + MI, diabetic + MI + 5 mg/kg sitagliptin, and diabetic + MI + 10 mg/kg sitagliptin. Isoproterenol in diabetic rats resulted in significant (p < 0.05) disturbance to the electrocardiogram, cardiac histopathological manifestations, and an increase in inflammatory markers compared with the vehicle and diabetic groups. Treatment with sitagliptin improved the electrocardiogram and histopathological sections, upregulated vascular endothelial growth factor (VEGF) and transmembrane phosphoglycoprotein protein (CD34) in cardiac tissues, and increased serum insulin-like growth factor 1 (IGF-1) and decreased cardiac tissue homogenate for interleukin 6 (IL-6) and cyclooxygenase 2 (COX-2). A relationship was found between serum IGF-1 and cardiac VEGF and CD34 accompanied by an improvement in cardiac function of diabetic rats with MI. Therefore, the observed effects of sitagliptin occurred at least partly through an improvement in angiogenesis and the mitigation of inflammation. Consequently, these data suggest that sitagliptin may contribute, in a dose-dependent manner, to protection against acute MI in diabetic individuals.

Adipose tissue-derived stem cells versus bone marrow-derived stem cells as an angiogenic therapy after ischemic limb injury in the adult male albino rat

ABSTRACTBackground: Peripheral arterial disease (PAD) remains one of the leading causes of deformity worldwide. Among various therapeutic options for PAD, stem cell-based therapies hold some great promises. Nonetheless, the therapeutic efficacy faces the limitation of poor survival of donor cells.The aim of this work: Isolation of the rat bone marrow MSCs (BM-MSCs) and adipose tissue MSCs (AD-MSCs) and assessing their growth kinetics and their role in improvement of angiogenesis after induction of acute hind limb ischemia through ligation of the femoral artery of the adult male albino rat.Material and Methods: The rat bone marrow and the adipose tissue were isolated from 10 male adult albino rats. They cultured and expanded through 6 passages. Acute lower limb ischemia was done by ligation of unilateral left sided femoral artery of an adult male albino rat. Both BM-MSCs and AD-MSCs, were injected immediately following ischemia in the semimembranosus muscle. BM-MSCs and AD-MSCs biological characteristics evaluated for cell therapy (morphology, flow cytometric analysis, colony-forming unit-fibroblast assay, proliferation capacity at passages 2, 4 and 6, population doubling time (PDT) and cell growth curves). Evaluation of muscle regeneration and angiogenesis was assessed through H&E staining of the tissue, Masson Trichrome to assess fibrosis, CD31 immunostaining for new blood vessel formation and electron microscopic examination for the cells ultrastructure.Results: BM-MSCs and AD-MSCs attached to the culture flask and displayed spindle-shaped morphology, more evident in AD-MSCs. Proliferation rate of AD-MSCs in the analyzed passages was more than BM-MSCs. The increase in the population doubling time (PDT) of both types of MSCs occurs with the increase in the number of passages. Light , electron microscopy and immunohistochemistry showed the better ability of AD-MSCs in improving the ischemic limb through their angiogenetic capacity than BM-MSCs.Conclusion: Rat AD- MSCs have growth kinetic advantages in the proliferative capacity,colony-forming unite fibroblast, population doubling time and angiogenic capacity when transplanted in a rat model of a hind limb ischemia more than that of BM-MSCs