Implantation of Autologous Stem Cells Derived from Adipose Tissue in Rat Bone Fractures

Stem cells derived from adipose tissue (ASCs) correspond to a major advance with respect to the bone regenerative medicine, as they have the ability for self-renewal, differentiation and paracrine stimulation to various types of tissues including bone and cartilage. The hypothesis of this study considers that fractures treated with ASCs, time decreases bone regeneration and vascularization increases, aiming to histologically evaluate bone regeneration and vascularization in these fractures. To accomplish this, 24 young male Sprague Dawley rats were used. The specimens were divided into two groups: Group A (treated) and group B (control). In both groups, the rats were euthanized at 11 and 21 days post-fracture. Statistically significant difference was observed in the number of newly formed trabeculae and vascular density in the treated group compared to control group concluded that rats treated with ASCs have a higher rate and better angiogenic bone regeneration, especially given the ability to synthesize components of the extracellular matrix of these cell, and the production of angiogenic growth factors.

Download Full-text

The Effect of Adipose Tissue-Derived Mesenchymal Stem Cells on Regeneration of Uterine Scars

Gynecology Obstetrics and Reproductive Medicine ◽

10.21613/gorm.2016.654 ◽

2017 ◽

Vol 23 (3) ◽

pp. 120

Author(s):

R. Ada Bender ◽

Aykan Yücel ◽

Volkan Noyan ◽

Aylin Gürpınar ◽

Pınar Atasoy ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Control Group ◽

Optimum Level ◽

Wound Recovery ◽

Significant Difference ◽

Histopathological Effects ◽

Mesenchyme Stem Cells

OBJECTIVE: The mesenchymal stem cell application to uterine healing scars may provide better tissue strength. STUDY DESIGN: Hysterectomy was performed on rats, and the wound recovery as a result of primary suturing was evaluated as tissue stretching and the positive histopathological effects. The mesenchymal stem cells originating from the adipose tissue were used during the healing period of the wound and would differentiate to mesenchyme-originated cells present in intact tissue for an optimum level of healing. RESULTS: The weights of non-incised uterine horns in the control group were found to be significantly higher than the weights of the incised uterine horns (z=2.52, p=0.012). In the experiment group, the weights of the incised uterine horns were found to be significantly higher than the non-incised uterine horns (z=2.527, p=0.012). In the control group, the non-incised uterine horns withstood the stretching test to a higher extent than the incised horns, and a significant difference was found between the stretching values (z=2.51, p=0.012). In the experiment group, the incised uterine horns withstood the stretching tests to a higher extent than the non-incised uterine horns; however, there was no significant difference between the stretching tests (z=1.540, p=0.123). CONCLUSION: Adipose tissue-originated mesenchyme stem cells were observed to increase the tissue stretching during wound healing.

Download Full-text

Paracrine Effect of Synovial-Derived Stem Cells on Induced Knee Osteoarthritis in Rats

Shiraz E-Medical Journal ◽

10.5812/semj.103268 ◽

2020 ◽

Vol In Press (In Press) ◽

Author(s):

Nader Tanideh ◽

Sara Sadat Nabavizadeh ◽

Soheil Ashkani-Esfahani ◽

Omid Koohi Hosseinabadi ◽

Parvin Ghaemmaghami ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Femoral Condyle ◽

Treatment Strategies ◽

Cell Group ◽

Control Group ◽

P Value ◽

Sprague Dawley ◽

Paracrine Effects ◽

Significant Difference

Background: Osteoarthritis (OA) is a progressive degenerative disease. Previous treatment strategies have tried to slow the progress of OA. Objectives: The present study aimed to stop and reverse the progressive nature of OA by the paracrine effects of synovial stem cells. Methods: Fifty male Sprague Dawley rats were randomly allocated to five equal groups (n = 10). The control group received no treatment. The second group received an intra-articular Hyalgan injection. The third group received an intra-articular injection of secreta. The fourth group received an intra-articular injection of synovial-derived stem cells (5 × 106). The last group received an intra-articular injection of secreta combined with synovial-derived stem cells (5 × 106). Three months after treatment, the samples were harvested and evaluated by histopathological and radiological analyses. Results: Histopathological and radiological findings demonstrated significant differences between the synovial stem cell combined with the secreta group and the control and Hyalgan groups. Significant differences were observed in the subchondral bone and matrix scores between the secreta group and the synovial stem cell and Hyalgan groups (P-value = 0.042 and P-value = 0.0001, respectively). Both secreta and synovial stem cell groups showed better healing in terms of cell population viability index than the Hyalgan group (P-value = 0.015 and P-value = 0.005, respectively). The synovial stem cell combined with secreta group showed a significant difference from the synovia stem cell group in both medial femoral condyle and fabella osteophyte indices (P-value = 0.004 and P-value = 0.011, respectively). Conclusions: The group treated with synovial stem cells combined with secreta showed better outcomes than other groups in histopathological and radiological evaluations.

Download Full-text

Adipose tissue-derived mesenchymal stem cells ameliorate experimental acute colitis in rats

10.21203/rs.3.rs-1036129/v1 ◽

2021 ◽

Author(s):

Seyed Jalil Masoumi ◽

Negar Hassanshahi ◽

Seyed-Mohammad Kazem Hosseini-Asl ◽

Davood Mehrabani ◽

Seyedeh-Sara Hashemi ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Therapeutic Potential ◽

Adipogenic Differentiation ◽

Control Group ◽

Sprague Dawley ◽

Acute Colitis ◽

Complete Treatment ◽

Anti Inflammatory

Abstract Complete treatment of ulcerative colitis (UC) is still difficult, while conventional therapies have various adverse effects. Mesenchymal stem cells (MSCs) have anti-inflammatory and immunomodulatory properties to be a therapeutic candidate for UC. We evaluated therapeutic potential of adipose tissue-derived mesenchymal stem cells (AdSCs) in treatment of an acute colitis rat model using histological and molecular assessments. Thirty male Sprague Dawley acetic acid-induced (2 mL of 3%) acute colitis rat models were randomly divided into three equal groups of control receiving 0.5 mL/kg of normal saline, sulfasalazine group receiving 500 mg/kg sulfasalazine and AdSCs group transplanted transrectally with 2×106 MSCs. They were evaluated histologically and by real time PCR for expression of apoptotic genes until 21 days. MSCs were spindle shape and positive for osteogenic and adipogenic differentiation. They displayed mesenchymal and lacked hematopoietic markers. In control group, severe inflammation, edema, ulcer, necrosis and infiltration of leukocytes were noticed. In sulfasalazine group, a moderate inflammation, edema, ulcer, necrosis and infiltration of leukocytes were visible; and in AdSCs group, mild inflammation, congestion, and infiltration of leukocytes were observed with a mild edema, but necrosis was absent in colonic tissue. A stronger decrease in expression of Bax, together with a higher increase in Bcl-2 was noted in AdSCs group. Based on histological and molecular findings, AdSCs were effective to ameliorate colitis lesions through their anti-inflammatory and anti-apoptotic activities showing that transplantation of AdSCS can be a potentially useful strategy in treatment of colitis.

Download Full-text

Octacalcium phosphate/gelatin composite facilitates bone regeneration of critical-sized mandibular defects in rats: A quantitative study

Journal of Dental Research Dental Clinics Dental Prospects ◽

10.15171/joddd.2019.040 ◽

2019 ◽

Vol 13 (4) ◽

pp. 258-266

Author(s):

Fereydoon Sargolzaei-Aval ◽

Eshagh Ali Saberi ◽

Mohammad Reza Arab ◽

Narjes Sargolzaei ◽

Tayebeh Sanchooli ◽

...

Keyword(s):

Bone Regeneration ◽

Volume Fraction ◽

Healing Process ◽

Octacalcium Phosphate ◽

Bone Defects ◽

Control Group ◽

Sprague Dawley ◽

Mandibular Bone ◽

Significance Level ◽

Significant Difference

Background. Regeneration of bone defects remains a challenge for maxillofacial surgeons. The present study aimed to compare the effects of octacalcium phosphate (OCP) and the combination of octacalcium phosphate/gelatin (OCP/Gel) on mandibular bone regeneration in rats Methods. In the present study, 36 male Sprague-Dawley rats were used. The animals were randomly assigned to the following experimental groups: OCP (n=12), OCP/Gel (n=12), and the control group (n=12). Defects were created in the rat mandibles and filled with 10 mg of OCP and OCP/Gel disks in the experimental groups. In the control group, however, no substance was administered. Samples were taken on days 7, 14, 21 and 56, respectively, after the implantation. Sections (5 µ) were prepared and stained by H&E. The sections were studied, and the volume fraction of newly formed bone was measured by Dunnett's T3 test based on the significance level (P=0.05). Results. In the experimental groups, the new bone formation began from the margin of defects 7‒14 days after the implantation. During the healing process, the newly formed bone healed a larger area of the defects and grew structurally. In the control group, the defects were primarily filled with dense connective tissue, and only a small amount of new bone was formed. The present study showed a statistically significant difference in the volume of newly formed bone between the experimental groups and the control group (P<0.001). Conclusion. OCP/Gel composite can be beneficial in the healing process of mandibular bone defects.

Download Full-text

Effect of volume flows on the viability of MSCs during injection through a cannula

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2021-2069 ◽

2021 ◽

Vol 7 (2) ◽

pp. 272-275

Author(s):

Lina Nießen ◽

Giulia Facchinetti ◽

Till Elsner ◽

Robert Wendlandt ◽

Timo Gemoll ◽

...

Keyword(s):

Stem Cells ◽

Statistical Analysis ◽

Bone Fractures ◽

Control Group ◽

Shear Forces ◽

Significance Level ◽

Non Union ◽

Injection Process ◽

Process Pressure ◽

Significant Difference

Abstract Introduction: Clinical trials currently evaluate the use of mesenchymal stem cells (MSCs) for the treatment of non-union bone fractures. The stem cells are injected directly into the non-union area of a bone via a cannula. During this injection process, pressure and shear forces affect the MSCs which could influence the viability of the cells. One parameter that influences the level of the shear forces is the volume flow. The aim of this study is to show whether the injection process with two different volume flows influences the cell viability. Methods: MSCs were isolated from bone tissue, harvested during arthroplasty. Afterwards, they were diluted to a concentration of 1 million cells/mL and 1 mL of this suspension was injected through a cannula with 200 mm length and 2 mm diameter (14 G) with volume flows of 38 and 100 mL/min. The evaluation was performed by detecting living, apoptotic, and dead cells using flow cytometry. The statistical analysis was performed with a Kruskal-Wallis-test to identify significant differences and with a TOST procedure for significant equivalence. The significance level was set to 5 % and the equivalence margin to 20 %. Results: The cell population of healthy cells was in the control group 85.88±2.98 %. After an injection with 38 mL/min the population of healthy cells was 86.04±2.53 % and with 100 ml/min 85.48±1.64 %. The statistical analysis revealed no significant difference between these groups (p = 0.99), but a significant equivalence between the control group and the two volume flows (38 mL/min: p = 0.002, 100 mL/min: p = 0.001). In addition the results show no increase of apoptotic and dead cells in the population after injection. Conclusion: The results indicate that the injection process through the cannula with these volume flows has no effect on the viability of the MSCs.

Download Full-text

The Effect of Single and Triple Testicular Biopsy Using Biopty Gun on Spermatogenesis in Pubertal Rats

Animals ◽

10.3390/ani11061569 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1569

Author(s):

Tomislav Šušnjar ◽

Ivana Kuzmić Prusac ◽

Ivan Švagelj ◽

Anđela Jurišić ◽

Tomislav Šušnjar ◽

...

Keyword(s):

Sperm Count ◽

Semen Analysis ◽

Study Groups ◽

Testicular Biopsy ◽

Male Rats ◽

Lower Percentage ◽

Control Group ◽

Sprague Dawley ◽

Left Testis ◽

Significant Difference

Background: The aim of this study was to compare consequences in single and triple testicular biopsy by biopty gun in pubertal rats using histological and immunohistochemical analysis. Methods: Thirty-two Sprague-Dawley male rats were used as the experimental model. The rats were randomly divided into three study groups. The rats from the first group (n = 12) received a single-biopsy of upper pole of the left testis, while the rats from the second group (n = 10) received triple-biopsy of upper and lower poles and lateral surface of left testis. The third group (n = 10) was a control group. On the eightieth day after the biopsy in all rats bilateral orchiectomy and funiculectomy were performed to obtain testicular tissue and sperm for analysis. The consequences of the puncture were observed by pathohistology, immunohistochemistry and semen analysis. Results: The results of the study showed lower percentage of sperm count (14.5 mill/mL vs. 16 mill/mL, p = 0.130), sperm motility (24.6% vs. 32.7%, p > 0.05), abnormal sperm (30% vs. 27%, p > 0.05), atrophic tubules (21% vs. 6%, p < 0.001), volume (1.7 mL vs. 2.28 mL, p < 0.01) and apoptotic index (1.56 vs. 1.19, p = 0.650) in the testes with a triple-biopsy compared to the testes with a single-biopsy. Semen analysis showed a borderline significant difference between the group with triple-biopsy where sperm count was lower than it in the control group (14.5 mill/mL vs. 17.5 mill/mL, p = 0.05). A single-biopsy has little effect on the testis, especially on overall fertility. A triple-biopsy showed higher degree of the testicular damage but without a significant impact on overall fertility. Semen analysis showed that single- and triple-biopsies did not have a significant effect on sperm count, motility and morphology. Conclusion: Biopty gun procedure is a cheap, simple and reliable method for testicular biopsy in rats without a significant effect on sperm count, motility and morphology.

Download Full-text

Clinical efficacy on glycemic control and safety of mesenchymal stem cells in patients with diabetes mellitus: Systematic review and meta-analysis of RCT data

PLoS ONE ◽

10.1371/journal.pone.0247662 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0247662

Author(s):

Jingjing He ◽

Desheng Kong ◽

Zhifen Yang ◽

Ruiyun Guo ◽

Asiamah Ernest Amponsah ◽

...

Keyword(s):

Diabetes Mellitus ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Treatment Group ◽

Random Effects ◽

Meta Analysis ◽

Cochrane Library ◽

Control Group ◽

Efficacy And Safety ◽

Significant Difference

Background Diabetes mellitus as a chronic metabolic disease is threatening human health seriously. Although numerous clinical trials have been registered for the treatment of diabetes with stem cells, no articles have been published to summarize the efficacy and safety of mesenchymal stem cells (MSCs) in randomized controlled trials (RCTs). Methods and findings The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to provide a reliable numerical summary and the most comprehensive assessment of therapeutic efficacy and safety with MSCs in diabetes. PubMed, Web of Science, Ovid, the Cochrane Library and CNKI were searched. The retrieval time was from establishment of these databases to January 4, 2020. Seven RCTs were eligible for analysis, including 413 participants. Meta-analysis results showed that there were no significant differences in the reduction of fasting plasma glucose (FPG) compared to the baseline [mean difference (MD) = -1.05, 95% confidence interval (CI) (-2.26,0.16), P<0.01, I2 = 94%] and the control group [MD = -0.62, 95%CI (-1.46,0.23), P<0.01, I2 = 87%]. The MSCs treatment group showed a significant decrease in hemoglobin (Hb) A1c [random-effects, MD = -1.32, 95%CI (-2.06, -0.57), P<0.01, I2 = 90%] after treatment. Additionally, HbA1c reduced more significantly in MSC treatment group than in control group [random-effects, MD = -0.87, 95%CI (-1.53, -0.22), P<0.01, I2 = 82%] at the end of follow-up. However, as for fasting C-peptide levels, the estimated pooled MD showed that there was no significant increase [MD = -0.07, 95%CI (-0.30, 0.16), P<0.01, I2 = 94%] in MSCs treatment group compared with that in control group. Notably, there was no significant difference in the incidence of adverse events between MSCs treatment group and control group [relative risk (RR) = 0.98, 95%CI (0.72, 1.32), P = 0.02, I2 = 70%]. The most commonly observed adverse reaction in the MSC treatment group was hypoglycemia (29.95%). Conclusions This meta-analysis revealed MSCs therapy may be an effective and safe intervention in subjects with diabetes. However, due to the limited studies, a number of high-quality as well as large-scale RCTs should be performed to confirm these conclusions.

Download Full-text

Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model

Zinc supplementation improves heme biosynthesis in rats exposed to lead ◽

10.18051/univmed.2021.v40.29-35 ◽

2021 ◽

Vol 40 (1) ◽

pp. 29

Author(s):

Nur Anna C Sa’dyah ◽

Agung Putra ◽

Bayu Tirta Dirja ◽

Nurul Hidayah ◽

Salma Yasmine Azzahara ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Growth Factor ◽

Liver Fibrosis ◽

Transforming Growth Factor ◽

Healing Process ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Significant Difference ◽

T1 And T2

Introduction Liver fibrosis (LF) results from the unregulated chronic wound healing process in liver tissue. Transforming growth factor-beta (TGF-β) is the major contributing cytokine of LF promotion through activation of quiescent hepatic stellate cells (HSCs) into myofibroblasts (MFs) and increased extracellular matrix (ECM) deposition such as collagen leading to scar tissue development. Mesenchymal stem cells (MSCs) have an immunomodulatory capability that could be used as a new treatment for repairing and regenerating LF through suppression of TGF-β. This study aimed to examine the role of MSCs in liver fibrosis animal models through suppression of TGF-β levels without scar formation particularly in the proliferation phase. Methods In this study, a completely randomized design was used with sample size of 24. Male Sprague Dawley rats were injected intraperitoneally (IP) with carbon tetrachloride (CCl4), twice weekly, for eight weeks to induce LF. Rats were randomly assigned to four groups: negative control, CCl4 group, and CCL4 + MSC-treated groups T1 and T2, at doses of 1 x 106 and 2x106 cells, respectively. TGF-β levels were analyzed by enzyme-linked immunosorbent assay (ELISA). One-way ANOVA and a least significant difference (LSD) was used to analyse the data. Results The TGF levels of LF rat models decreased on day 7 after MSC administration. The levels of TGF-β in both MSC groups T1 and T2 decreased significantly compared with the control group (p<0.05). The TGF-β suppression capability of T2 was optimal and more significant than that of T1. Conclusion MSCs can suppress TGF levels in liver fibrosis induced rats.

Download Full-text

Micro-Computed Tomography Analysis on Administration of Mesenchymal Stem Cells - Bovine Teeth Scaffold Composites for Alveolar Bone Tissue Engineering

Journal of Biomimetics Biomaterials and Biomedical Engineering ◽

10.4028/www.scientific.net/jbbbe.52.86 ◽

2021 ◽

Vol 52 ◽

pp. 86-96

Author(s):

Desi Sandra Sari ◽

Fourier Dzar Eljabbar Latief ◽

Ferdiansyah ◽

Ketut Sudiana ◽

Fedik Abdul Rantam

Keyword(s):

Computed Tomography ◽

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Regeneration ◽

Bone Growth ◽

Alveolar Bone ◽

Micro Computed Tomography ◽

Freeze Dried ◽

Significant Difference

The tissue engineering approach for periodontal tissue regeneration using a combination of stem cells and scaffold has been vastly developed. Mesenchymal Stem Cells (MSCs) seeded with Bovine Teeth Scaffold (BTSc) can repair alveolar bone damage in periodontitis cases. The alveolar bone regeneration process was analyzed by micro-computed tomography (µ-CT) to observe the structure of bone growth and to visualize the scaffold in 3-Dimensional (3D). The purpose of this study is to analyze alveolar bone regeneration by µ-CT following the combination of MSCs and bovine teeth scaffold (MSCs-BTSc) implantation in the Wistar rat periodontitis model. Methods. MSCs were cultured from adipose-derived mesenchymal stem cells of rats. BTSc was taken from bovine teeth and freeze-dried with a particle size of 150-355 µm. MSCs were seeded on BTSc for 24 hours and transplanted in a rat model of periodontitis. Thirty-five Wistar rats were made as periodontitis models with LPS induction from P. gingivalis injected to the buccal section of interproximal gingiva between the first and the second mandibular right-molar teeth for six weeks. There were seven groups (control group, BTSc group on day 7, BTSc group on day 14, BTSc group on day 28, MSCs-BTSc group on day 7, MSCs-BTSc group on day 14, MSCs-BTSc group on day 28). The mandibular alveolar bone was analyzed and visualized in 3D with µ-CT to observe any new bone growth. Statistical Analysis. Group data were subjected to the Kruskal Wallis test followed by the Mann-Whitney (p <0.05). The µ-CT qualitative analysis shows a fibrous structure, which indicates the existence of new bone regeneration. Quantitative analysis of the periodontitis model showed a significant difference between the control model and the model with the alveolar bone resorption (p <0.05). The bone volume and density measurements revealed that the MSCs-BTSc group on day 28 formed new bone compared to other groups (p <0.05). Administration of MSCs-BTSc combination has the potential to form new alveolar bone.

Download Full-text

Efficacy and Safety of Intravenous Mesenchymal Stem Cells for Ischemic Stroke

Neurology ◽

10.1212/wnl.0000000000011440 ◽

2021 ◽

pp. 10.1212/WNL.0000000000011440

Author(s):

Jong-Won Chung ◽

Won Hyuk Chang ◽

Oh Young Bang ◽

Gyeong Joon Moon ◽

Suk Jae Kim ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Controlled Trial ◽

Outcome Evaluation ◽

Autologous Serum ◽

Secondary Outcome ◽

Control Group ◽

Link Type ◽

Significant Difference ◽

Major Stroke

ObjectiveTo test whether autologous modified mesenchymal stem cells (MSCs) improve recovery in patients with chronic major stroke.MethodsIn this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct within 90 days of symptom onset were assigned, in a 2:1 ratio, to receive preconditioned autologous MSC injections (MSC group) or standard treatment alone (control group). The primary outcome was the score on the modified Rankin Scale (mRS) at 3 months. The secondary outcome was to further demonstrate motor recovery.ResultsA total of 39 and 15 patients were included in the MSC and control groups, respectively, for the final intention-to-treat analysis. Mean age of patients was 68 (range, 28–83) years, and mean interval between stroke onset to randomization was 20.2 (range, 5–89) days. Baseline characteristics were not different between groups. There was no significant difference between the groups in the mRS score shift at 3 months (p = 0.732). However, secondary analyses showed significant improvements in lower extremity motor function in the MSC group compared to the control group (change in the leg score of the Motricity Index, p = 0.023), which was notable among patients with low predicted recovery potential. There were no serious, treatment-related adverse events.ConclusionsIntravenous application of preconditioned, autologous MSCs with autologous serum was feasible and safe in patients with chronic major stroke. MSC treatment was not associated with improvements in the 3-month mRS score, but we did observe leg motor improvement in detailed functional analyses.Classification of evidenceThis study provides Class III evidence that autologous mesenchymal stem cells do not improve 90-day outcomes in patients with chronic stroke.Trial registrationclinicaltrials.gov Identifier: NCT01716481.

Download Full-text