Umbilical Cord Blood-derived Mesenchymal Stem Research Articles

Advancing Regenerative Cellular Therapies in Non-Scarring Alopecia

Alopecia or baldness is a common diagnosis in clinical practice. Alopecia can be scarring or non-scarring, diffuse or patchy. The most prevalent type of alopecia is non-scarring alopecia, with the majority of cases being androgenetic alopecia (AGA) or alopecia areata (AA). AGA is traditionally treated with minoxidil and finasteride, while AA is treated with immune modulators; however, both treatments have significant downsides. These drawbacks compel us to explore regenerative therapies that are relatively devoid of adverse effects. A thorough literature review was conducted to explore the existing proven and experimental regenerative treatment modalities in non-scarring alopecia. Multiple treatment options compelled us to classify them into growth factor-rich and stem cell-rich. The growth factor-rich group included platelet-rich plasma, stem cell-conditioned medium, exosomes and placental extract whereas adult stem cells (adipose-derived stem cell-nano fat and stromal vascular fraction; bone marrow stem cell and hair follicle stem cells) and perinatal stem cells (umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs), Wharton jelly-derived MSCs (WJ-MSCs), amniotic fluid-derived MSCs (AF-MSCs), and placental MSCs) were grouped into the stem cell-rich group. Because of its regenerative and proliferative capabilities, MSC lies at the heart of regenerative cellular treatment for hair restoration. A literature review revealed that both adult and perinatal MSCs are successful as a mesotherapy for hair regrowth. However, there is a lack of standardization in terms of preparation, dose, and route of administration. To better understand the source and mode of action of regenerative cellular therapies in hair restoration, we have proposed the “À La Mode Classification”. In addition, available evidence-based cellular treatments for hair regrowth have been thoroughly described.

Immunomodulatory Effect of Epidermal Growth Factor Secreted by Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells on Atopic Dermatitis.

Background and ObjectivesHuman mesenchymal stem cells (MSCs) are emerging as a treatment for atopic dermatitis (AD), a chronic inflammatory skin disorder that affects a large number of people across the world. Treatment of AD using human umbilical cord blood-derived MSCs (hUCB-MSCs) has recently been studied. However, the mechanism underlying their effect needs to be studied continuously. Thus, the objective of this study was to investigate the immunomodulatory effect of epidermal growth factor (EGF) secreted by hUCB-MSCs on AD.Methods and ResultsTo explore the mechanism involved in the therapeutic effect of MSCs for AD, a secretome array was performed using culture medium of hUCB-MSCs. Among the list of genes common for epithelium development and skin diseases, we focused on the function of EGF. To elucidate the effect of EGF secreted by hUCB-MSCs, EGF was downregulated in hUCB-MSCs using EGF-targeting small interfering RNA. These cells were then co-cultured with keratinocytes, Th2 cells, and mast cells. Depletion of EGF disrupted immunomodulatory effects of hUCB-MSCs on these AD-related inflammatory cells. In a Dermatophagoides farinae-induced AD mouse model, subcutaneous injection of hUCB-MSCs ameliorated gross scoring, histopathologic damage, and mast cell infiltration. It also significantly reduced levels of inflammatory cytokines including interleukin (IL)-4, tumor necrosis factor (TNF)-α, thymus and activation-regulated chemokine (TARC), and IL-22, as well as IgE levels. These therapeutic effects were significantly attenuated at all evaluation points in mice injected with EGF-depleted hUCB-MSCs.ConclusionsEGF secreted by hUCB-MSCs can improve AD by regulating inflammatory responses of keratinocytes, Th2 cells, and mast cells.

CD26 Inhibition Potentiates the Therapeutic Effects of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells by Delaying Cellular Senescence.

Mesenchymal stem cells (MSCs) are recognized as potential treatments for multiple degenerative and inflammatory disorders as a number of animal and human studies have indicated their therapeutic effects. There are also several clinically approved medicinal products that are manufactured using these cells. For such large-scale manufacturing requirements, the in vitro expansion of harvested MSCs is essential. Multiple subculturing of MSCs, however, provokes cellular senescence processes which is known to deteriorate the therapeutic efficacy of the cells. Strategies to rejuvenate or selectively remove senescent MSCs are therefore highly desirable for fostering future clinical applications of these cells. In this present study, we investigated gene expression changes related to cellular senescence of MSCs derived from umbilical cord blood and found that CD26, also known as DPP4, is significantly upregulated upon cellular aging. We further observed that the inhibition of CD26 by genetic or pharmacologic means delayed the cellular aging of MSCs with their multiple passaging in culture. Moreover, the sorting and exclusion of CD26-positive MSCs from heterogenous cell population enhanced in vitro cell attachment and reduced senescence-associated cytokine secretion. CD26-negative MSCs also showed superior therapeutic efficacy in mouse lung emphysema model. Our present results collectively suggest CD26 is a potential novel target for the rejuvenation of senescent MSCs for their use in manufacturing MSC-based applications.

Optimization of human umbilical cord blood-derived mesenchymal stem cell isolation and culture methods in serum- and xeno-free conditions

BackgroundAlthough umbilical cord blood (UCB) is identified as a source of mesenchymal stem cells (MSCs) with various advantages, the success in cell isolation is volatile. Therefore, it is necessary to optimize methods of cord blood-derived MSC (UCB-MSC) isolation and culture. In this study, we evaluated the efficiency of UCB-MSC isolation and expansion using different commercially available serum- and xeno-free media and investigated the capacity of autologous serum and plasma as a supplement to support cell proliferation. Additionally, we defined the presence of multilineage-differentiating stress-enduring (Muse) cells in the UCB-MSC population. Functions of UCB-MSC in in vitro angiogenesis processes and anti-cancer were also verified.MethodsMononuclear cells were isolated using density gradient separation and cultured in four commercial media kits, as well as four surface coating solutions. UCB-MSCs were characterized and tested on tube formation assay, and co-cultured with SK-MEL cells in a transwell system.ResultsThe results showed that only StemMACS™ MSC Expansion Media is more appropriate to isolate and culture UCB-MSCs. The cells exhibited a high cell proliferation rate, CFU forming capability, MSC surface marker expression, trilineage differentiate potential, and chromosome stability. In addition, the culture conditions with autologous serum coating and autologous plasma supplement enhanced cell growth and colony forming. This cell population contained Muse cells at rate of 0.3%. Moreover, UCB-MSCs could induce the tube formation of human umbilical vein endothelial cells and inhibit more than 50% of SK-MEL cell growth.ConclusionsUCB-MSCs could be high-yield isolated and expanded under serum- and xeno-free conditions by using the StemMACS™ MSC Expansion Media kit. Autologous serum coating and plasma supplement enhanced cell proliferation. These UCB-MSCs had effected the tube formation process and an anti-cancer impact.

Human umbilical cord blood mesenchymal stem cells-derived exosomal microRNA-503-3p inhibits progression of human endometrial cancer cells through downregulating MEST.

Endometrial cancer (EC) is a group of epithelial malignant tumors that occur in the endometrium. The specific pathogenesis is not revealed, hence, the goal of this study was to investigate the influence of human umbilical cord blood mesenchymal stem cells (hUMSCs)-derived exosomal microRNA-503-3p (miR-503-3p) on human EC cells by mediating mesoderm-specific transcript (MEST). The binding relationship between MiR-503-3p and MEST was searched. HUMSCs were collected and exosomes (Exos) were isolated and identified. Human EC cell lines HEC-1B and RL95-2 were transfected with elevated miR-503-3p or silenced MEST vector or co-cultured with Exos to figure their roles in biological functions of EC cells. The in vitro effect of miR-503-3p, MEST, and Exos on EC cells was further verified in vivo. MEST was a target of miR-503-3p. Overexpression of miR-503-3p or reduction of MEST suppressed the biological functions of EC cells. Enhanced MEST expression mitigated the role of upregulated miR-503-3p on the growth of EC cells. HUMSCs-derived Exos suppressed EC cell growth, upregulated miR-503-3p-modified HUMSCs-derived Exos had a more obvious inhibitory effect on EC cell growth. The anti-tumor effect of elevated miR-503-3p, silenced MEST, and HUMSCs-derived Exos were verified in nude mice. This study highlights that hUMSCs-derived exosomal miR-503-3p inhibits EC development by suppressing MEST, which is of great benefit to EC therapy.

Safety of an allogeneic, human, umbilical cord blood-derived mesenchymal stem cells-4% hyaluronate composite for cartilage repair in the knee

IntroductionKnee osteoarthritis treatments that functionally restore diseased/damaged cartilage are limited. ObjectiveTo evaluate the safety and effectiveness of allogeneic, human, umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) + 4% hyaluronate composite for knee cartilage defects. MethodsIn a 24-month, open-label, non-randomized phase 1/2a study, adults ≥18 years with single, full-thickness, ICRS grade 3 to 4 knee cartilage defects were recruited sequentially based on initial defect size (Dose A: 2-5 cm2; Dose B: >5 cm2). The hUCB-MSCs composite (0.25 × 107 cells/cm2) was surgically implanted into the defects. Safety (adverse events [AEs] and dose-limiting toxicities) was the primary objective, and efficacy was secondary. ResultsTwelve patients (mean 38 years; 83% male; BMI 27.6 kg/m2) completed the study. All patients reported ≥1 treatment-emergent AE (TEAE): 42 with Dose A (n = 6); 27 with Dose B (n = 6); most common were decreased range of motion (100%) and arthralgia (92%). Seven patients (58%) had 10 treatment-related TEAEs. No discontinuations due to TEAEs, serious AEs, or deaths were reported. There were no dose-limiting toxicities; maximum tolerated dose was established as 2.0 × 107 cells. The IKDC score and other knee function and pain scores significantly improved from baseline to months 12 and 24. Clinically significant abnormal MRI findings declined from 91.7% (n = 11) at baseline to 16.7% (n = 2) at month 24. ConclusionhUCB-MSCs + 4% hyaluronate composite implantation appears to be safe over 24 months in US patients with ICRS grade 3 to 4 knee cartilage defects, with improvements in function, pain, and cartilage repair evidence.

Mesenchymal stem cell-derived exosomes inhibit the VEGF-A expression in human retinal vascular endothelial cells induced by high glucose.

To determine the effect of exosomes derived from human umbilical cord blood mesenchymal stem cells (hUCMSCs) on the expression of vascular endothelial growth factor A (VEGF-A) in human retinal vascular endothelial cells (HRECs). Exosomes were isolated from hUCMSCs using cryogenic ultracentrifugation and characterized by transmission electron microscopy, Western blotting and nanoparticle tracking analysis. HRECs were randomly divided into a normal control group (group A), a high glucose model group (group B), a high glucose group with 25 µg/mL (group C), 50 µg/mL (group D), and 100 µg/mL exosomes (group E). Twenty-four hours after coculture, the cell proliferation rate was detected using flow cytometry, and the VEGF-A level was detected using immunofluorescence. After coculture 8, 16, and 24h, the expression levels of VEGF-A in each group were detected using PCR and Western blots. The characteristic morphology (membrane structured vesicles) and size (diameter between 50 and 200 nm) were observed under transmission electron microscopy. The average diameter of 122.7 nm was discovered by nanoparticle tracking analysis (NTA). The exosomal markers CD9, CD63, and HSP70 were strongly detected. The proliferation rate of the cells in group B increased after 24h of coculture. Immunofluorescence analyses revealed that the upregulation of VEGF-A expression in HRECs stimulated by high glucose could be downregulated by cocultured hUCMSC-derived exosomes (F=39.03, P<0.01). The upregulation of VEGF-A protein (group C: F=7.96; group D: F=17.29; group E: F=11.89; 8h: F=9.45; 16h: F=12.86; 24h: F=42.28, P<0.05) and mRNA (group C: F=4.137; group D: F=13.64; group E: F=22.19; 8h: F=7.253; 16h: F=16.98; 24h: F=22.62, P<0.05) in HRECs stimulated by high glucose was downregulated by cocultured hUCMSC-derived exosomes (P<0.05). hUCMSC-derived exosomes downregulate VEGF-A expression in HRECs stimulated by high glucose in time and concentration dependent manner.

Immunomodulatory Effect of Human Umbilical Cord Blood-derived Mesenchymal Stem Cells on Activated T-lymphocyte.

Many studies have been performed about regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) and their application in different treatment approaches. The present study aimed to investigate the immunomodulatory effect of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) on the gene expression profile of cytokines in stimulated T-lymphocytes. For this purpose, MSCs were isolated from umbilical cord blood samples and cultured in Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine serum. The nature of MSCs was identified by flow cytometry analysis and differentiation to the adipocyte and osteocyte lineage. Moreover, to investigate the immunomodulatory effects of MSCs on T cells, a co-culture system was designed and expression levels of interleukin (IL)-2, IL-4, IL-6, IL-10,IL-13, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-β) genes were measured; using the real-time polymerase chain reaction (RT-PCR) technique. Our results demonstrated the ability of MSCs to differentiate into adipocyte and osteocyte lineages. Further investigation also displayed that although UCB-MSCs could significantly reduce the expression of pro-inflammatory cytokines like IL-2, IL-6, IFN-γ, and TNF-α in activated T-lymphocytes, they noticeably potentiated the expression levels of IL-4, IL-10, IL-13, and TGF-β in the co-culture setting. In conclusion, UCB-MSCs have immunomodulatory effects on activated T-lymphocytes in favor of anti-inflammatory responses.

Exosomes Secreted by Umbilical Cord Blood-Derived Mesenchymal Stem Cell Attenuate Diabetes in Mice.

Mesenchymal stem cell (MSC) therapy is an innovative approach in diabetes due to its capacity to modulate tissue microenvironment and regeneration of glucose-responsive insulin-producing cells. In this study, we investigated the role of MSC-derived exosomes in pancreatic regeneration and insulin secretion in mice with streptozotocin-induced diabetes. Mesenchymal stem cells (MSCs) were isolated and characterized from umbilical cord blood (UCB). Exosomes were isolated and characterized from these MSCs. Diabetes was induced in male C57Bl/6 mice by streptozotocin (STZ; 40 mg/kg body weight, i.p.) for five consecutive days. The diabetic mice were administered (i.v.) with MSC (1 × 105 umbilical cord blood MSC cells/mice/day), their derived exosomes (the MSC-Exo group that received exosomes derived from 1 × 105 MSC cells/mice/day), or the same volume of PBS. Before administration, the potency of MSCs and their exosomes was evaluated in vitro by T cell activation experiments. After day 7 of the treatments, blood samples and pancreatic tissues were collected. Histochemistry was performed to check cellular architecture and β cell regeneration. In body weight, blood glucose level, and insulin level, cell proliferation assay was done to confirm regeneration of cells after MSC and MSC-Exo treatments. Hyperglycemia was also attenuated in these mice with a concomitant increase in insulin production and an improved histological structure compared to mice in the PBS-treated group. We found increased expression of genes associated with tissue regeneration pathways, including Reg2, Reg3, and Amy2b in the pancreatic tissue of mice treated with MSC or MSC-Exo relative to PBS-treated mice. MicroRNA profiling of MSC-derived exosomes showed the presence of miRs that may facilitate pancreatic regeneration by regulating the Extl3-Reg-cyclinD1 pathway. These results demonstrate a potential therapeutic role of umbilical cord blood MSC-derived exosomes in attenuating insulin deficiency by activating pancreatic islets' regenerative abilities.

158&#x2003;Umbilical cord blood-derived mesenchymal stem cells (UCB-MSC) used for the prevention of metritis in cattle.

Reproduction, Fertility and Development is an international journal publishing original research , review and comment in the fields of reproduction and developmental biology in humans, domestic animals and wildlife

AACE2021-A-1055: Efficacy of Umbilical Cord Blood-Derived Stem Cells Transplantation Versus Their Conditioned Media in Hypothyroid Rats on Thyroid Function and Structure

Primary hypothyroidism is a chronic condition with significant morbidity. Providing physiological thyroid hormone replacement through pharmacological treatment remains controversial. Aim of work: To assess the efficacy of human umbilical cord blood-derived mesenchymal stem cells (UM-MSCs) transplantation versus their conditioned media (CM) on thyroid function tests (TFTs) and thyroid structure in hypothyroid rats, also to compare intravenous versus its intranasal route.

Treatment of Radiation Bone Injury with Transplanted hUCB-MSCs via Wnt/β-Catenin.

Radiation-induced bone injury (RIBI) is one of the complications after radiotherapy for malignant tumors. However, there are no effective measures for the treatment of RIBI in clinical practice, and the mechanism of RIBI is unclear. We use a single high-dose ionizing radiation (6Gy) to analyze the effect of radiotherapy on osteoblast function. Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) were cocultured with irradiated osteoblasts to examine their therapeutic effects and mechanisms on osteoblast injury. The hUCB-MSC transplantation mouse model is used to confirm the in vivo role of hUCB-MSC treatment in radiation bone injury. Western blot analysis, qRT-PCR, immunohistochemistry, and immunofluorescence staining were used to analyze gene expression and angiogenesis. The apoptosis and migration of osteoblasts were measured by Hoechst staining, scratch test, and transwell. The differentiation of osteoblasts was measured by ALP and Alizarin red staining and transmission electron microscopy. The bone-related parameters of mice were evaluated by micro-CT analysis. We found that radiation can damage the DNA of osteoblasts; induce apoptosis; reduce the differentiation, migration, and adhesion of osteoblasts, leading to lipogenesis of bone marrow mesenchymal stem cells (BMSCs) and reducing the source of osteoblasts; and increase the number of osteoclasts in bone tissue, while MSC treatment prevents these changes. Our results reveal the inhibitory effect of radiation on osteoblast function. hUCB-MSCs can be used as a therapeutic target for the development of new therapeutic strategies for radiotherapy of bone injury diseases.

OR45. Improving the migratory function of endothelial progenitor cells under high glucose conditions via engineering with human umbilical cord blood mesenchymal stem cell-derived secretome

Abstract Aims Human umbilical cord blood mesenchymal stem cells (hUCB-MSC) secreted a group of paracrine factors known as secretome. It has the ability to promote neovascularization and angiogenesis, and it is thought to be capable of modulating EPC function. The capability of hUCB-MSCs-derived secretome in enhancing EPC migration under high glucose condition, which is expected to mimic the metabolic disturbance that occurs in patients with type 2 diabetes mellitus, has been not yet established. This study aims to elucidate the effect of Human Umbilical Cord Blood Mesenchymal Stem Cell (hUCB-MSCs)-derived secretome on the EPCs migration under high glucose conditions. Method and Results EPCs were isolated from peripheral blood samples of chronic coronary syndrome patient and cultured for three days. Cultured EPCs were incubated with high glucose for five days and were treated with secretome at various concentration. The migration of EPCs was assessed using the Transwell migration assay. hUCB-MSC-derived secretome induced the migration capability of EPC with at least 20% concentration of secretome, this effect was more potent under high glucose conditions with the least concentration of secretome was 10% (p &amp;lt; 0.001). The migratory function of EPCs was intact on short term exposure of high glucose. Conclusion Our finding suggest that hUCB-MSCs-derived secretome may enhance migratory function of EPCs under high glucose conditions. hUCB-MSCs-derived secretome may serve as a promising cell-free regenerative therapy.

OR18. Combination of ramiprilat and human umbilical cord blood-mesenchymal stem cells derived secretome increase endothelial progenitor cells migration

Abstract Background and Aims Stem cells therapy has been studied in the cardiovascular field, but the limitations in terms of survival and risk of rejection make cell-free therapy with secretome worth considering. This study aims to identify the effect of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) derived secretome, ramiprilat, and combination of both on endothelial progenitor cells (EPCs) migration. Methods and Results EPCs were collected from mononuclear cells (MNCs) of the peripheral blood of chronic coronary syndrome patient using density gradient centrifugation method, then cultured in Stemline II medium (Sigma Aldrich, USA). Secretom was made by taking the supernatant from the hUCB-MSCs cell line culture media that had been centrifuged. Cultured EPCs was divided into control group, treatment with 10 µmol Ramiprilat, various concentrations of hUCB-MSCs-derived secretome (2%, 10%, and 20%) and combination of 10 µmol Ramiprilat and each concentration of secretome. EPCs migration was assessed using Boyden chamber assay. Results showed that ramiprilat and all doses of secretome increased EPCs migration compared to the control group (p &amp;lt; 0.001). Secretome 20% had higher EPCs migration than ramiprilat (51.00±5.15 vs 33.80±2.49, p &amp;lt; 0.001), and the combination of ramiprilat and secretome 20% showed the highest number of migrated EPCs among all groups. Conclusion hUCB-MSCs-derived secretome and ramiprilat increase EPCs migration. The combination of those two substances furtherly increased the migrated cells. hUCB-MSCs-derived secretome has the potential as a cell-free cardiovascular treatment for coronary artery disease patients.

OR40. Human umbilical cord blood-mesenchymal stem cell-derived secretome in combination with atorvastatin enhances endothelial progenitor cells proliferation and migration: an insight for new coronary artery disease therapeutic

Abstract Aims Human umbilical cord blood-mesenchymal stem cell (hUCB-MSC)-derived secretome is known to be able to promote neovascularization and angiogenesis, so it is also thought to have a capability to modulate endothelial progenitor cell (EPC) functions. Atorvastatin is the cornerstone of coronary artery disease (CAD) treatment which can enhance EPCs proliferation and migration. This study aims to analyze the effect of the hUCB-MSC-derived secretome and its combination with atorvastatin toward EPCs proliferation and migration. Methods EPCs were isolated from a CAD patient’s peripheral blood. Cultured EPCs were divided into a control group and treatment group of 2.5 µM atorvastatin, hUCB-MSC-derived secretome (2%, 10%, and 20% concentration) and its combination. EPCs proliferation was evaluated using an MTT cell proliferation assay, and EPC migration was evaluated using a Transwell migration assay kit. Results This research showed that hUCB-MSC-derived secretomes significantly increase EPC proliferation and migration in a dose-dependent manner. The high concentration of hUCB-MSC-derived secretome were shown to be superior to atorvastatin in inducing EPC proliferation (OD, 1.585±0.029 vs 0.738±0.025; p &amp;lt; 0.001) and migration (51.00±5.15 vs 34.40±3.05, p &amp;lt; 0.001). Combination of the hUCB-MSC-derived secretome and atorvastatin shown to improve EPCs proliferation and migration compared to hUCB-MSC-derived secretome treatment or atorvastatin alone (p &amp;lt; 0.001). Conclusions This study concluded that the hUCB-MSC-derived secretome work synergistically with atorvastatin treatment in improving CAD patient-derived EPCs proliferation and migration. Hence, it could be the basis for secretome as the new CAD treatment modality.

OR12. Augmentation of endothelial progenitor cell proliferation in stable coronary artery disease subjects using human umbilical cord blood-mesenchymal stem cell-derived secretome in hyperglycemia condition

Abstract Background and Aims The number of endothelial progenitor cells (EPC) was decreased in stable coronary artery disease (SCAD) and diabetic patients. Human umbilical cord blood-mesenchymal stem cell-derived secretome (secretome) has the potential to improve the proliferation of EPC. This study aims to figure out the effect of the secretome on EPC proliferation of SCAD patients and hyperglycemia conditions. Method and Results EPC’s were isolated from peripheral blood samples and cultured for three days in the Stemline II medium. Cultured EPC’s were incubated with various concentrations of secretome (2%, 10%, and 20%). The other groups were treated with high glucose (25 mmol/L), a combination of secretome and high glucose, vascular endothelial growth factors-only (positive group), and the basal medium only (negative group). MTT cell proliferation assay kit was used to evaluate the EPC’s proliferation at 72 hours after reagent addition. The absorbance of MTT was measured in optical density (OD). The 20% secretome group was significantly higher than the positive control group (1.59 vs. 1.43; p &amp;lt; 0.001). EPC proliferation in the secretome group is dose-dependent manner. EPC’s proliferation of the high glucose group was significantly lower than the negative control group (0.65 vs. 0.89; p &amp;lt; 0.001). EPCs proliferation OD was significantly higher between a combination of 20% secretome and high glucose than the secretome-only group (1.78 vs. 1.59; p &amp;lt; 0.001). Conclusion The secretome enhances the EPC proliferation of SCAD patients, even in a high glucose condition. The secretome is a new potential substance to modulate the EPC proliferation of SCAD patients.

Dry arthroscopy with a simple retraction technique for knee joint cartilage repair using allogenic human umbilical cord blood-derived mesenchymal stem cells

Mesenchymal stem cell treatment has become more widely available and has shown promising potential for the repair of knee articular cartilage defects. More recently, open arthrotomy has been performed via a para-patellar incision for cartilage repair using allogenic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). However, arthroscopy allows better visualization and leads to earlier gain of the range of motion and less scar formation than open arthrotomy, especially in the knee joint. In this study, we present an easy and effective technique for arthroscopic hUCB-MSCs implantation without any special equipment.

Granulomatous Reaction to Dermal Injection of Growth Factors from Umbilical Cord Blood-Derived Mesenchymal Stem Cells: A Case Report

Use of stem cells to treat various diseases in dermatology has been of interest. Conditioned media with the growth factors secreted from stem cells has been used as a topical agent. We report a case of foreign body granulomas that appeared days after dermal injection of the conditioned media mimicking scars at all injection sites.

Outcomes of human umbilical cord blood-derived mesenchymal stem cells in enhancing tendon-graft healing in anterior cruciate ligament reconstruction: an exploratory study

BackgroundThe study investigated whether allogeneic human umbilical cord blood-derived MSCs (hUCB-MSCs) could be safely used without treatment-related adverse events, reducing tunnel enlargement, and improve clinical results in human anterior cruciate ligament (ACL) reconstruction.MethodsThirty patients were enrolled consecutively. They were divided into three groups by randomization. In the negative control group, ACL reconstruction surgery without additional treatment was performed. In the experimental group, a hUCB-MSC and hyaluronic acid mixture was applied to the tendon-bone interface of the femoral tunnels during ACL reconstruction surgery. In the positive control group, only hyaluronic acid was applied. Finally, 27 patients were analyzed after the exclusion of three patients. The incidence of treatment-related adverse events, clinical outcomes, including second-look arthroscopic findings, and the amount of tunnel enlargement, were evaluated.ResultsThere were no treatment-related adverse events in the treatment groups. Tunnel enlargement in the experimental group (579.74 ± 389.85 mm3) was not significantly different from those in the negative (641.97 ± 455.84 mm3) and positive control (421.96 ± 274.83 mm3) groups (p = 0.6468). There were no significant differences between the groups in clinical outcomes such as KT-2000 measurement (p = 0.793), pivot shift test (p = 0.9245), International Knee Documentation Committee subjective score (p = 0.9195), Tegner activity level (p = 0.9927), and second-look arthroscopic findings (synovial coverage of the graft, p = 0.7984; condition of the graft, p = 0.8402).ConclusionsAllogeneic hUCB-MSCs were used safely for ACL reconstruction without treatment-related adverse event in a 2-year follow-up. However, our study did not suggest any evidence to show clinical advantage such as the prevention of tunnel enlargement postoperatively and a decrease in knee laxity or improvement of clinical outcomes.Trial registrationCRIS, Registration Number: KCT0000917. Registered on 12 November 2013; https://cris.nih.go.kr/cris/index.jsp

Effects of single and multiple transplantations of human umbilical cord mesenchymal stem cells on the recovery of ovarian function in the treatment of premature ovarian failure in mice

BackgroundCurrently, there is no effective treatment for premature ovarian failure (POF), and stem cell therapy is considered the most promising treatment. Human umbilical cord blood mesenchymal stem cells (hUC-MSCs) have shown good regenerative ability in various diseases, including POF; however, their underlying mechanism and dosage for POF treatment remain unclear. This study aimed to compare the effect of single and multiple injections of hUC-MSCs on ovarian function repair in chemotherapy-induced POF.MethodsFemale mice were intraperitoneally injected with 30 mg/kg busulfan and 120 mg/kg cyclophosphamide (CTX) to induce POF. In the single hUC-MSC injection group, hUC-MSCs were transplanted into mice D7 after CTX and busulfan administration, while in the multiple injection group, hUC-MSCs were transplanted on D7, D14, and D21 after CTX and busulfan administration. We evaluated the ovarian morphology, fertility, follicle-stimulating hormone and estradiol concentrations, follicle count, POF model, and cell transplantation results. In addition, real-time polymerase chain reaction, immunohistochemistry, and miRNA and mRNA chips were used to evaluate the effect of the cell therapy.ResultsOvary size, number of follicle at all developmental stages, and fertility were significantly reduced in the POF group compared with the control. Under hUC-MSC treatment, the ovarian morphology and follicle count were significantly restored, and fertility was significantly increased. By comparing the single and multiple hUC-MSC injection groups, we found that the anti-Müllerian hormone and Ki-67 levels were significantly increased in the multiple hUC-MSC group on D60 after chemotherapy. The expression of stimulating hormone receptors, inhibin α, and inhibin β was significantly restored, and the therapeutic effect was superior to that of the single hUC-MSC injection group.ConclusionThese results indicate that hUC-MSCs can restore the structure of injured ovarian tissue and its function in chemotherapy-induced POF mice and ameliorate fertility. Multiple hUC-MSC transplantations have a better effect on the recovery of ovarian function than single hUC-MSC transplantation in POF.