Umbilical Cord-derived Stem Cells Research Articles

Stem Cells and Bone Tissue Engineering.

Segmental bone defects that are caused by trauma, infection, tumor resection, or osteoporotic fractures present significant surgical treatment challenges. Host bone autograft is considered the gold standard for restoring function but comes with the cost of harvest site comorbidity. Allograft bone is a secondary option but has its own limitations in the incorporation with the host bone as well as its cost. Therefore, developing new bone tissue engineering strategies to treat bone defects is critically needed. In the past three decades, the use of stem cells that are delivered with different scaffolds or growth factors for bone tissue engineering has made tremendous progress. Many varieties of stem cells have been isolated from different tissues for use in bone tissue engineering. This review summarizes the progress in using different postnatal stem cells, including bone marrow mesenchymal stem cells, muscle-derived stem cells, adipose-derived stem cells, dental pulp stem cells/periodontal ligament stem cells, periosteum stem cells, umbilical cord-derived stem cells, peripheral blood stem cells, urine-derived stem cells, stem cells from apical papilla, and induced pluripotent stem cells, for bone tissue engineering and repair. This review also summarizes the progress using exosomes or extracellular vesicles that are delivered with various scaffolds for bone repair. The advantages and disadvantages of each type of stem cell are also discussed and explained in detail. It is hoped that in the future, these preclinical results will translate into new regenerative therapies for bone defect repair.

Mesenchymal stem cell therapy in retinitis pigmentosa patients: A systematic review

The current systematic review was aimed at exploring the mesenchymal stem cell (MSC) therapy in retinitis pigmentosa (RP) patients. This study included all the studies which focused and reported the Mesenchymal stem cell therapy in retinitis pigmentosa patients. A filtration procedure was used to remove duplicates, irrelevant publications. The online databases Ovid MEDLINE, Ovid Embase, and the Cochrane Library were used to perform a literature search for publications published between 2016 and 2023, without any date or language restrictions. We used a combination of relevant search terms "MSC, MSC transplantation, Stem cell therapy, Bone marrow-derived stem cell, Adipose tissue-derived stem cell, umbilical cord-derived stem cell, and RP". We independently identified publications and systematically screened titles, abstracts, and full texts of the collected publications. Eleven trials were evaluated, comprising two preclinical and nine clinical trials assessing mesenchymal stem cells derived from adipose tissue, bone marrow, umbilical cord, and Warton jelly cells. The effectiveness and outcomes of MSC treatment for retinitis pigmentosa varied among different types of MSCs used in therapy. However, the weak evidence regarding the safety of MSCs challenges their promise as a potential treatment for retinitis pigmentosa.

Effect of mesenchymal stromal cells transplantation on the outcomes of patients with knee osteoarthritis: A systematic review and meta-analysis.

Cell therapy has been explored as a new regenerative treatment for osteoarthritis in the field of regenerative medicine. However, the efficacy of stem cell transplantation from different sources for the treatment of knee osteoarthritis (KOA) remains controversial. This study integrates and evaluates the previously published data of stem cell transplantation for KOA to explore the curative effect of different stem cells. We conducted a meta-analysis of randomized controlled trials on stem cell therapy for KOA. Measures of efficacy included Visual Analog Scale (VAS), Lequesne index, Lysholm Knee Scoring Scale (LKSS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Joint injury was evaluated through the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. We analyzed 16 studies involving 875 KOA patients. The stem cell treatment showed significant VAS reduction from the third month onwards. Subgroup analysis suggested the most significant pain relief at different postoperative months came from adipose-derived and umbilical cord-derived stem cells. Autologous adipose tissue resulted in better pain alleviation compared with allogenic. However, autologous bone marrow stem cells did not show increased pain relief over allogeneic ones. Combination therapy (HA and/or PRP) showed no effect. Autologous adipose-derived stem cells demonstrate the most effective recovery of knee joint function. In WORMS assessment, there was no significant difference between the stem cell group and control. Stem cell transplantation proved safe and effective for KOA treatment. Different sources stem cells have a good effect on alleviating knee joint pain, restoring knee joint function, and minimizing patient trauma.

Recent clinical trials with stem cells to slow or reverse normal aging processes.

Aging is associated with a decline in the regenerative potential of stem cells. In recent years, several clinical trials have been launched in order to evaluate the efficacy of mesenchymal stem cell interventions to slow or reverse normal aging processes (aging conditions). Information concerning those clinical trials was extracted from national and international databases (United States, EU, China, Japan, and World Health Organization). Mesenchymal stem cell preparations were in development for two main aging conditions: physical frailty and facial skin aging. With regard to physical frailty, positive results have been obtained in phase II studies with intravenous Lomecel-B (an allogeneic bone marrow stem cell preparation), and a phase I/II study with an allogeneic preparation of umbilical cord-derived stem cells was recently completed. With regard to facial skin aging, positive results have been obtained with an autologous preparation of adipose-derived stem cells. A further sixteen clinical trials for physical frailty and facial skin aging are currently underway. Reducing physical frailty with intravenous mesenchymal stem cell administration can increase healthy life expectancy and decrease costs to the public health system. However, intravenous administration runs the risk of entrapment of the stem cells in the lungs (and could raise safety concerns). In addition to aesthetic purposes, clinical research on facial skin aging allows direct evaluation of tissue regeneration using sophisticated and precise methods. Therefore, research on both conditions is complementary, which facilitates a global vision.

Umbilical Cord–Derived Stem Cells for the Treatment of Knee Osteoarthritis: A Systematic Review

Background:The use of mesenchymal stem cells (MSCs) for the treatment of knee osteoarthritis (OA) has gained recent interest in the orthopaedics community.Purpose:To review the literature to evaluate the efficacy of umbilical cord–derived MSCs in the treatment of OA of the knee joint.Study Design:Systematic review; Level of evidence, 4.Methods:We searched the PubMed, Cochrane Library, and Embase databases to identify studies with evidence levels from 1 to 4 that evaluated the clinical efficacy of human umbilical cord–derived MSC (hUC-MSC) injections for knee OA. The search phrase used was “umbilical cord knee osteoarthritis.” In the studies reviewed, patients were assessed based on the macroscopic International Cartilage Regeneration & Joint Preservation Society (ICRS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale (VAS) for pain, and the subjective International Knee Documentation Committee (IKDC) score.Results:A total of 7 studies met inclusion criteria, including 385 patients undergoing injection of hUC-MSCs (mean age, 59.7 years). The mean follow-up was 23.4 months. Weighted averages of the WOMAC, macroscopic ICRS, subjective IKDC, and VAS scores all showed improvement from before to after treatment. No severe adverse reactions were recorded.Conclusion:Patients undergoing treatment of knee OA with hUC-MSCs might be expected to experience improvements in clinical outcomes. Additional high-quality randomized studies are needed to better determine the efficacy of hUC-MSC for the treatment of knee OA.

Fractional laser-assisted administration of human umbilical cord mesenchymal stem cells to reduce hypertrophic scars in rabbit ears.

The formation of hypertrophic scar is due to the abnormal accumulation and remodeling of the extracellular matrix, especially collagen tissue. Our research was designed to investigate the treatment effect of different administrations of human umbilical cord-derived stem cells and to hypertrophic scars on rabbit ears. Thirty New Zealand female white rabbits were treated as hypertrophic scar models. PBS was injected into the scars on the right ear of each group as control, while human umbilical cord-derived stem cells or condition medium of human umbilical cord-derived stem cells were administrated into the left ear through subcutaneous injection or fractional laser-assisted administration. Gross examination, scar elevation index (SEI) calculation and sampling were executed 5 weeks after administration. Then H&E and Masson staining analysis and the expression levels detections of α-SMA, Collagen I, TGF-β1, IL-1β, and IL-6 were performed. Our results demonstrated that the severity of hyperplasia was lower than the model group after stem cells and conditioned medium treatment. H&E and Masson staining results showed that the inflammation in scars was greatly alleviated and the degree of fibrosis was reduced after treatment. There was no significant difference in the therapeutic effect between subcutaneous injection or fractional laser-assisted administration. Both stem cells and conditioned medium can down-regulate SEI and factors expression levels in all groups. However, compared with the stem cells, the therapeutic effects of the conditioned medium were lower. The results confirmed that stem cells had an available treatment effect on hypertrophic scars of rabbit ears. In addition to the paracrine pathway, stem cells may have other ways to treat hypertrophic scars. Fractional laser-assisted administration may become a potential administration of stem cell clinical application in the future.

Comparative evaluation of proliferative potential and replicative senescence associated changes in mesenchymal stem cells derived from dental pulp and umbilical cord.

Mesenchymal stem cells (MSC) have been widely studied for tissue regeneration and cell-based therapy. MSC can be isolated from different body tissues while several biological waste sources like dental pulp, umbilical cord, cord derived blood, amniotic fluid or urine have also emerged as potential sources of MSCs. Specifically, isolation of MSCs from such non-conventional sources show promising outcomes due to the non-invasiveness of the extraction process and high proliferation capacity of the isolated MSC. However, these stem cells also exhibit the limitation of replicative senescence in long-term culture condition. Inter-cellular reactive oxygen species is an important contributor for inducing cellular senescence under long-term culture conditions. For translational application, it becomes imperative to compare the stem cells isolated from these sources for their senescence and proliferative properties. In this study, MSC were extracted from two different sources of biological waste materials-dental pulp and umbilical cord, and compared for their proliferation capacity and replicative senescence at different passage numbers (i.e. P2 and P6). Intracellular ROS production was significantly (p < 0.001) less in dental pulp stem cells culture in comparison to umbilical cord-derived stem cells at P6. The β-gal expression also showed significantly (p < 0.001) low expression in DPSC culture compared to that of UCSC at P6. The study indicates the source of stem cells influences the proliferation capacity as well as replicative senescence of MSCs. This study will thus pave the path of future research in selecting appropriate stem cell source for regenerative medicine application.

A Review of Placenta and Umbilical Cord-Derived Stem Cells and the Immunomodulatory Basis of Their Therapeutic Potential in Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a devastating lung disorder of preterm infants as a result of an aberrant reparative response following exposures to various antenatal and postnatal insults. Despite sophisticated medical treatment in this modern era, the incidence of BPD remains unabated. The current strategies to prevent and treat BPD have met with limited success. The emergence of stem cell therapy may be a potential breakthrough in mitigating this complex chronic lung disorder. Over the last two decades, the human placenta and umbilical cord have gained increasing attention as a highly potential source of stem cells. Placenta-derived stem cells (PDSCs) and umbilical cord-derived stem cells (UCDSCs) display several advantages such as immune tolerance and are generally devoid of ethical constraints, in addition to their stemness qualities. They possess the characteristics of both embryonic and mesenchymal stromal/stem cells. Recently, there are many preclinical studies investigating the use of these cells as therapeutic agents in neonatal disease models for clinical applications. In this review, we describe the preclinical and clinical studies using PDSCs and UCDSCs as treatment in animal models of BPD. The source of these stem cells, routes of administration, and effects on immunomodulation, inflammation and regeneration in the injured lung are also discussed. Lastly, a brief description summarized the completed and ongoing clinical trials using PDSCs and UCDSCs as therapeutic agents in preventing or treating BPD. Due to the complexity of BPD, the development of a safe and efficient therapeutic agent remains a major challenge to both clinicians and researchers.

Umbilical cord derived mesenchymal stem cell therapy for osteonecrosis of femoral head

Osteo Necrosis of the Femoral Head (ONFH) is a form of osteonecrosis that occurs owing to interruption of blood supply to the proximal femur followed by fragmentation, reossification, and remodelling of the femoral head. In United States, the incidence of avascular necrosis of the femoral head is projected to be around 30000, which contributes to 10% of the total hip replacement done every year. It was believed that necrosis of proximal femur occurs due to the inadequate supply of progenitor cells in the femoral head. So, treatment is aimed at introducing stem cells in necrosis area in order to avoid the risk of fracture and collapse to restore the structural design of femoral head. The objective of this review is to highlight the potential of mesenchymal stem cell (MSC) therapy along with core decompression for the management of ONFH with a special reference to umbilical cord-derived stem cells. Keywords: Umbilical cord, Mesenchymal stem cells, Osteonecrosis, Femoral head, Avascular necrosis.

Role of stem cells in the management of acute kidney disease

Background and aim Renal failure is usually treated by hemodialysis forever. Renal transplantation is the only curative intervention. However, regenerative therapies are expected to exert a beneficial role in such situations. The aim of this study was to study the role of mesenchymal stem cells (MSCs) in the treatment of acute renal failure (ARF) in an animal model. Materials and methods ARF was induced by cisplatin injection in 20 male rats weighing 200–225 g. Rats were allocated into one of two equal groups: group A included 10 rats with ARF and umbilical cord-derived stem cell treatment, and group B included 10 rats with saline treatment. In addition, 10 healthy rats were included as a healthy control group (group C). Both serum urea and creatinine were measured after induction of renal failure and on the 7th and 15th day after MSC treatment. Kidney sections were obtained, stained with hematoxylin and eosin, and examined histologically. Results Serum urea and creatinine showed marked elevation after cisplatin injection. These values progressively decreased with MSC treatment significantly. At the end of the second week, the values were near normal. In addition, histological examination of renal section confirms the results obtained by laboratory analysis. Conclusion Umbilical cord-derived MSCs could play a regenerative action in ARF.

Therapeutic efficacy of umbilical cord-derived stem cells for diabetes mellitus: a meta-analysis study

BackgroundStem cell therapy provides great hope for patients with diabetes mellitus (DM). DM is a seriously alarming metabolic disease characterized by hyperglycemia and β cell dysfunction. Efficient novel therapeutic modalities to treat DM are indeed warranted. Stem cells (SC) derived from the umbilical cord specifically provide several advantages and unique characteristics being a readily available non-invasive source, with an additional credit for their banking potential. This meta-analysis study aims to provide a focused assessment for therapeutic efficacy of umbilical cord (UC)-derived SC-transplantation, namely Wharton’s jelly mesenchymal stem cells (WJ-MSCs) and umbilical cord blood (UCB) for DM.MethodsThe clinical efficacy was evaluated based on glycemic control status (reflected on HbA1c%) and β cell function (reflected on C-peptide levels), as well as the daily insulin requirement in diabetic patients after receiving UC-derived SC-transplantation compared to baseline values. Moreover, we assessed these outcome measures in patients who received such intervention compared to those who did not receive it in randomized/non-randomized controlled clinical trials. We employed a random-effects model and standardized mean difference for this meta-analysis.ResultsEleven eligible clinical studies were included; WJ-MSCs (6 studies; 172 patients including 71 controls) and UCB (5 studies; 74 patients including 15 controls). WJ-MSCs significantly improved HbA1c% (pooled-estimate − 1.085; 95%CI (− 1.513, − 0.657); p < 0.001) and C-peptide levels (pooled-estimate 1.008; 95%CI (0.475, 1.541); p < 0.001), as well as the daily insulin-requirement (pooled-estimate − 2.027; 95%CI (− 3.32, − 0.733); p = 0.002). On the contrary, UCB was found to be uniformly ineffective; HbA1c% (pooled-estimate − 0.091, 95%CI (− 0.454, 0.271); p = 0.622), significantly deteriorated C-peptide levels (pooled-estimate − 0.789; 95%CI (− 1.252, − 0.325); p < 0.001) and daily insulin-requirement (pooled-estimate 0.916; 95%CI (0.247, 1.585); p = 0.007). All these observations remained consistent when we carried out sub-group meta-analysis for T1DM and T2DM and also when we compared patients who received WJ-MSCs or UCB to controls.ConclusionsThe results of our meta-analysis provide a clear evidence for the superior efficacy of WJ-MSCs over UCB in DM. This sheds lights on the importance to consider banking of WJ-MSCs together with the well-established routine UCB-banking, especially for those with family history of DM. Additionally, further clinical studies are required to investigate therapeutic efficacy of selected/enriched UCB-derived cell populations with immunomodulatory/regenerative potential in DM.

Mesenchymal stem cells - a promising strategy for treating knee osteoarthritis.

AimsThe purpose of our study was to determine whether mesenchymal stem cells (MSCs) are an effective and safe therapeutic agent for the treatment of knee osteoarthritis (OA), owing to their cartilage regeneration potential.MethodsWe searched PubMed, Embase, and the Cochrane Library, with keywords including “knee osteoarthritis” and “mesenchymal stem cells”, up to June 2019. We selected randomized controlled trials (RCTs) that explored the use of MSCs to treat knee OA. The visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), adverse events, and the whole-organ MRI score (WORMS) were used as the primary evaluation tools in the studies. Our meta-analysis included a subgroup analysis of cell dose and cell source.ResultsSeven trials evaluating 256 patients were included in the meta-analysis. MSC treatment significantly improved the VAS (mean difference (MD), –13.24; 95% confidence intervals (CIs) –23.28 to –3.20, p = 0.010) and WOMAC (MD, –7.22; 95% CI –12.97 to –1.47, p = 0.010). The low-dose group with less than 30 million cells showed lower p-values for both the VAS and WOMAC. Adipose and umbilical cord–derived stem cells also had lower p-values for pain scores than those derived from bone marrow.ConclusionOverall, MSC-based cell therapy is a relatively safe treatment that holds great potential for OA, evidenced by a positive effect on pain and knee function. Using low-dose (25 million) and adipose-derived stem cells is likely to achieve better results, but further research is needed.Cite this article: Bone Joint Res 2020;9(10):719–728.

Growth factors-based beneficial effects of platelet lysate on umbilical cord-derived stem cells and their synergistic use in osteoarthritis treatment

Poor viability of mesenchymal stem cells (MSCs) at the transplanted site often hinders the efficacy of MSCs-based therapy. Platelet lysate (PL) contains rich amounts of growth factors, which benefits cell growth. This study aimed to explore how human PL benefits umbilical cord-derived MSCs (huc-MSCs), and whether they have synergistic potential in osteoarthritis (OA) treatment. As quality control, flow cytometry and specific staining were performed to identify huc-MSCs, and ELISA was used to quantify growth factors in PL. CCK-8 and flow cytometry assays were performed to evaluate the effects of PL on the cell viability and cell cycle progression of huc-MSCs. Wound healing and transwell assays were conducted to assess the migration of huc-MSCs. RNA sequencing, real time PCR, and Western blot assays were conducted to explore the growth factors-based mechanism of PL. The in vitro results showed that PL significantly promoted the proliferation, cell cycle, and migration of huc-MSCs by upregulating relevant genes/proteins and activating beclin1-dependent autophagy via the AMPK/mTOR signaling pathway. The main growth factors (PDGF-AA, IGF-1, TGF-β, EGF, and FGF) contributed to the effects of PL in varying degrees. The in vivo data showed that combined PL and huc-MSCs exerted significant synergistic effect against OA. The overall study determined the beneficial effects and mechanism of PL on huc-MSCs and indicated PL as an adjuvant for huc-MSCs in treating OA. This is the first report on the growth factors-based mechanism of PL on huc-MSCs and their synergistic application. It provides novel knowledge of PLʹs roles and offers a promising strategy for stem cell-based OA therapy by combining PL and huc-MSCs.

Red Deer Umbilical Cord-Derived Stem Cell Conditioned Media Combined With Ablative Resurfacing of the Face.

Laser resurfacing is the gold standard procedure for photodamage, but is not without downtime and risk. Use of periprocedural products containing stem cell conditioned media may improve results and optimize healing. This was a prospective, randomized controlled, double-blind study, evaluating the efficacy and tolerability of red deer umbilical cord-derived stem cell conditioned media (USCCM) cream and serum pre- and post- ablative facial resurfacing. Twenty patients with moderate to severe photodamage were randomized to receive vehicle or USCCM cream and serum pre- and post- ablative resurfacing of the face. Blinded investigators rated healing, tolerability, and efficacy, while subjects rated post-procedure symptoms, tolerability, and satisfaction. Both the active and vehicle pre-procedure cream were soothing, calming and easy to use by all patients. There was a trend towards decreased facial erythema and crusting in the active versus vehicle group. A greater improvement in wrinkling occurred in the active group. The majority of subjects were very satisfied with the active products. There were no serious adverse events. Red deer umbilical cord-derived stem cell conditioned media (USCCM) is well tolerated, safe and efficacious for use pre- and post- facial laser resurfacing.J Drugs Dermatol. 2020;19(11): 1044-1048 doi:10.36849/JDD.2020.5246.

Impact of human umbilical cord–derived stem cells (HUMSCs) on host responses to a synthetic polypropylene mesh for pelvic floor reconstruction in a rat model

In order to evaluate the effects of human umbilical cord-derived stem cells (HUMSCs) on the biocompatibility of and tissue response to a polypropylene (PP) mesh (Gynemesh™ PS) implanted in rat vaginas, HUMSCs were isolated and characterized in vitro and then combined with Gynemesh™ PS to create a tissue-engineered mesh. This tissue-engineered mesh and pure PP mesh were implanted in the submucosae of the posterior vaginal walls of rats. Mesh/tissue complexes were harvested at 1, 4 and 12weeks after implantation. Histological evaluations including an assessment of the inflammatory reaction, neovascularization and fibrosis around the mesh fibers were performed and real-time quantitative polymerase chain reaction (RT-PCR) was used to analyze the mRNA expression of genes involved in wound healing at the tissue-mesh interface. After being seeded onto the PP mesh scaffold, HUMSCs grew and proliferated well in vitro culture. One week after implantation, the HUMSC-seeded mesh elicited a greater inflammatory response than the pure PP mesh (3.33 ± 0.21 vs. 2.63 ± 0.18, p = 0.026), while 4 and 12weeks after implantation, the inflammatory response in the HUMSC-seeded mesh was lower than that in the unseeded mesh (p < 0.05). At 12weeks, the HUMSC-seeded mesh induced a lower expression of matrix metalloproteinase (MMP)-1 and a higher expression of anti-inflammatory cytokine interleukin (IL)-4. HUMSCs may decrease the inflammatory response and improve the biocompatibility of a conventional synthetic mesh and may have the potential to reduce postoperative complications such as mesh exposure or erosion.

Linc02349 promotes osteogenesis of human umbilical cord-derived stem cells by acting as a competing endogenous RNA for miR-25-3p and miR-33b-5p.

ObjectivesIncreasing evidences suggest that inducing mesenchymal stem cells to differentiate into osteoblasts has been as an especially important component in the prevention and therapy for degenerative bone disease. Here, we identify a novel lncRNA, linc02349, which increases significantly during osteogenic differentiation.Materials and methodsHuman umbilical cord‐derived stem cells (hUC‐MSCs) and dental pulp mesenchymal stem cells were used. Overexpression and knockdown of linc02349 in cell lines were generated using lentiviral‐mediated gene delivery method. Bioinformatics prediction, Ago2‐RIP assay and dual‐luciferase reporter system were employed to examine miRNA which interacts with linc02349. The RNA FISH assay was performed to identify the subcelluar location of linc02349. Alizarin Red S staining, ALP staining and qPCR were applied to identify the osteogenic differentiation. The potential linc02349‐regulated genes, miR‐25‐3p and miR‐33b‐5p, were explored by ChIP, RIP and Western blotting assays. Micro‐CT was used to measure the osteogenic content in bone formation assay in vivo.ResultsLinc02349 overexpression improves osteogenic differentiation by in vitro and in vivo analysis. Mechanistically, linc02349 acts as a molecular sponge for miR‐25‐3p and miR‐33b‐5p to control expression abundance of SMAD5 and Wnt10b, respectively, which eventually activated Dlx5/OSX pathway and hence promoted osteogenic differentiation. In addition, we revealed that STAT3 interacts with linc02349 promoter region and positively regulates the linc02349 transcriptional activity.ConclusionThese findings identify that linc02349 modulates the osteogenic differentiation through acting as a sponge RNA of miR‐25‐3p and miR‐33b‐5p and regulating SMAD5 and Wnt10b, and proposed a new interaction between STAT3 and linc02349, which could be a potential target in the process the osteogenesis of hUC‐MSCs for future clinical application.

Antioxidant pretreatment enhances umbilical cord derived stem cells survival in response to thermal stress in vitro.

Aim: Pretreatment of stem cells with antioxidants accelerates their ability to counter oxidative stress and is associated with the overall therapeutic outcome of their transplantation. Material & methods: Wharton Jelly derived mesenchymal stem cells (WJMSCs) were cultured and pretreated with various doses of antioxidants; Vitamin C (Vit C), Vitamin E (Vit E), Vitamin D3 (Vit D3) and their Cocktail, followed by exposure to in vitro heat injury. Assessment of WJMSCs survival, paracrine release, in vitro wound healing and expression of angiogenic and survival markers was conducted. Results: The results displayed an enhanced survival of WJMSCs especially in the case of Cocktail priming. Conclusion: Our data suggest that antioxidant pretreatment of WJMSCs strengthens the endurance of the cells, within stress conditions.

Human adipose tissue- and umbilical cord-derived stem cells: which is a better alternative to treat spinal cord injury?

Multiple types of stem cells have been proposed for the treatment of spinal cord injury, but their comparative information remains elusive. In this study, a rat model of T10 contusion spinal cord injury was established by the impactor method. Human umbilical cord-derived mesenchymal stem cells (UCMSCs) or human adipose tissue-derived mesenchymal stem cells (ADMSCs) (2.5 μL/injection site, 1 × 105 cells/μL) was injected on rostral and caudal of the injury segment on the ninth day after injury. Rats injected with mesenchymal stem cell culture medium were used as controls. Our results show that although transplanted UCMSCs and ADMSCs failed to differentiate into neurons or glial cells in vivo, both significantly improved motor and sensory function. After spinal cord injury, UCMSCs and ADMSCs similarly promoted spinal neuron survival and axonal regeneration, decreased glial scar and lesion cavity formation, and reduced numbers of active macrophages. Bio-Plex analysis of spinal samples showed a specific increase of interleukin-10 and decrease of tumor necrosis factor α in the ADMSC group, as well as a downregulation of macrophage inflammatory protein 3α in both UCMSC and ADMSC groups at 3 days after cell transplantation. Upregulation of interleukin-10 and interleukin-13 was observed in both UCMSC and ADMSC groups at 7 days after cell transplantation. Isobaric tagging for relative and absolute quantitation proteomics analyses showed that UCMSCs and ADMSCs induced changes of multiple genes related to axonal regeneration, neurotrophy, and cell apoptosis in common and specific manners. In conclusion, UCMSC and ADMSC transplants yielded quite similar contributions to motor and sensory recovery after spinal cord injury via anti-inflammation and improved axonal growth. However, there were some differences in cytokine and gene expression induced by these two types of transplanted cells. Animal experiments were approved by the Laboratory Animal Ethics Committee at Jinan University (approval No. 20180228026) on February 28, 2018, and the application of human stem cells was approved by the Medical Ethics Committee of Medical College of Jinan University of China (approval No. 2016041303) on April 13, 2016.

Intra-Articular Umbilical Cord Derived Mesenchymal Stem Cell Therapy for Chronic Elbow Osteoarthritis in Dogs: A Double-Blinded, Placebo-Controlled Clinical Trial.

Background: Intra-articular stem cell therapy may help alleviate lameness caused by osteoarthritis in dogs. Umbilical cord-derived stem cell (UMSC) therapy has not yet been investigated in a veterinary clinical study. We hypothesized that dogs treated with intra-articular UMSC will have improved limb function and quality of life when compared to dogs treated with a saline placebo injection.Methods: This was a prospective, double-blinded, placebo-controlled clinical trial in client-owned dogs with chronic elbow osteoarthritis with a follow-up time of 6 months. Dogs were assigned to receive intra-articular UMSC (n = 38) or a saline placebo intra-articular injection (n = 30). Outcome measures included the Canine Brief Pain Inventory score (CBPI) and peak vertical force (PVF) from force-platform gait analysis. Treatment was considered successful when there was a decrease in the Pain Severity Score of at least one and a decrease in the Pain Interference Score of at least one from baseline. Success rates and PVF were compared between groups.Results: No adverse effects associated with UMSC were noted. Of the dogs completing the study, treatment success in the UMSC (n = 28) vs. placebo groups (n = 23) was observed in 54 vs. 28% of dogs at 1 month, 50 vs. 27% at 3 months, and 46 vs. 14% at 6 months, respectively. Success rate in the UMSC group was significantly higher than the placebo group at 1 and 6 months after treatment. However, no differences in PVF of the affected limb over time was observed in either group.Conclusions: Intra-articular UMSC for osteoarthritis may improve clinical signs based on owner observations.

Is There a Noninvasive Source of MSCs Isolated with GMP Methods with Better Osteogenic Potential?

Background A new trend in the treatment for alveolar clefts in patients with cleft lip and palate involves the use of bone tissue engineering strategies to reduce or eliminate the morbidity associated with autologous bone grafting. The use of mesenchymal stem cells—autologous cells obtained from tissues such as bone marrow and fat—combined with various biomaterials has been proposed as a viable option for use in cleft patients. However, invasive procedures are necessary to obtain the mesenchymal stem cells from these two sources. To eliminate donor site morbidity, noninvasive stem cell sources such as the umbilical cord, orbicularis oris muscle, and deciduous dental pulp have been studied for use in alveolar cleft bone tissue engineering. In this study, we evaluate the osteogenic potential of these various stem cell types. Methods Ten cellular strains obtained from each different source (umbilical cord, orbicularis oris muscle, or deciduous dental pulp) were induced to osteogenic differentiation in vitro, and the bone matrix deposition of each primary culture was quantified. To evaluate whether greater osteogenic potential of the established mesenchymal stem cell strains was associated with an increase in the expression profile of neural crest genes, real-time qPCR was performed on the following genes: SRY-box 9, SRY-box 10, nerve growth factor receptor, transcription factor AP-2 alpha, and paired box 3. Results The mesenchymal stem cells obtained from deciduous dental pulp and orbicularis oris muscle demonstrated increased osteogenic potential with significantly more extracellular bone matrix deposition when compared to primary cultures obtained from the umbilical cord after twenty-one days in culture (p = 0.007 and p = 0.005, respectively). The paired box 3 gene was more highly expressed in the MSCs obtained from deciduous dental pulp and orbicularis oris muscle than in those obtained from the umbilical cord. Conclusion These results suggest that deciduous dental pulp and orbicularis oris muscle stem cells demonstrate superior osteogenic differentiation potential relative to umbilical cord-derived stem cells and that this increased potential is related to their neural crest origins. Based on these observations, and the distinct translational advantage of incorporating stem cells from noninvasive tissue sources into tissue engineering protocols, greater study of these specific cell lines in the setting of alveolar cleft repair is indicated.