Umbilical Cord Blood Mesenchymal Stem Cells Research Articles

The Cytokine Levels of Cord Blood- and Wharton's Jelly-Derived Mesenchymal Stem Cells from Early to Late Passages.

Mesenchymal stem cells (MSCs) are promising for clinical studies owing to their self-renewal, multipotency, trophic, and immunomodulatory properties. This study aimed to investigate the cytokine levels of human umbilical cord blood (CB) and Wharton's Jelly-(WJ) derived MSCs relevant to immune modulation on different passage levels in vitro. Umbilical CB MSCs were isolated using the ficoll-paque gradient method, and WJ-MSCs were isolated by the explant method. After isolation, the MSCs were characterized using flow cytometry. The supernatant cytokine levels (interferon-gamma (IFN-γ), interleukin 4 (IL-4), interleukin 17 (IL-17)) of MSCs at each passage were evaluated using the ELISA assay. MSCs exhibited different cytokine levels with each passage number. In WJ-MSC culture supernatants, IL-17 levels significantly increased at P4 and P5 compared to the first passage (p < 0.005), while the other passages showed a decrease. IFN-γ levels increased at passage P1 and P4 and decreased at other passages (p < 0.005). IL-4 levels significantly increased only at passage P3 (p < 0.005). In CB-MSC culture supernatants, IL-17 and IL-4 cytokines decreased compared to P0, while IFN-γ cytokine increased from P0 (p < 0.005). The changing ratio of cytokine levelsfor both CB-MSCs and WJ-MSCs were similarly maintained from early to late passages. More research is needed to understand the immunomodulatory functions of MSCs.

Effect of human umbilical cord blood-mesenchymal stem cells on cisplatin-induced nephrotoxicity in rats.

Cisplatin-containing regimen is an effective treatment for several malignancies. However, cisplatin is an important cause of nephrotoxicity. So, many trials were performed to transplant stem cells systemically or locally to control cisplatin-induced nephrotoxicity. Stem cell therapeutic effect may be dependent on the regulation of inflammation and oxidant stress. To investigate the effect of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) on the histological structure, the oxidant stress, and the inflammatory gene expression in an experimental model of cisplatin-induced nephrotoxicity in rats. The rats were divided into 6 equal groups (each of 10 rats): Group I included normal rats that received no treatment. Group II included healthy rats that received IV hUCB-MSCs. Group III included untreated cisplatin-induced nephrotoxic rats. Group IV included cisplatin-induced nephrotoxic rats that received magnesium (Mg) injections after injury. Group V was injected with hUCB-MSCs after injury. Group VI received both Mg and hUCB-MSCs after injury. In tissue homogenates, reduced glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) activities were measured. Quantitative real-time-polymerase chain reaction (qRT-PCR) was performed to assess iNOS, TLR4, and NF-kB gene expression. Hematoxylin and eosin (H&E) staining was performed to study the histological structure of the kidney. Immunohistochemical staining of iNOS and NF-κB was performed, as well. Disturbed kidney functions, oxidative status, and histological structure were seen in the rats that received cisplatin. Treated groups showed improvements in kidney functions, oxidative status, and histological structure, particularly in the combined treatment group. In the cisplatin-induced nephrotoxicity model, hUCB-MSCs could improve the functional and morphological kidney structure by modulation of oxidative and inflammatory status.

BRONCHOPULMONARY DYSLASIA OF NEWBORNS AND PROSPECTS OF CELL THERAPY IN UKRAINE AND WORLDWIDE

Introduction. Premature birth is a serious challenge for modern medicine – in the world, about 14.9 million babies are born before 37 weeks of pregnancy, which is approximately 11.0% of all newborns. Bronchopulmonary dysplasia (BLD) is the most common form of chronic lung disease that affects premature babies and contributes to their morbidity and mortality. BPD develops in approximately 25.0% of infants with a birth weight of less than 1,500 g. Among infants born at less than 28 weeks' gestational age, the overall incidence of BPD is estimated to be 48–68%. The limited possibilities of BPD pharmacotherapy prompted the search for new therapeutic approaches. One of the alternatives is biological therapy based on mesenchymal stem cells (MSCs), secretome of MSCs, cryopreserved tissue extracts, etc.&#x0D; The aim of the study: to characterize current information on the therapeutic potential of mesenchymal stem cells in the treatment of newborns with bronchopulmonary dysplasia.&#x0D; Materials and methods. Publications were selected based on the databases PubMed, Clinical Key Elsevier, Cochrane Library, eBook Business Collection, and Google Scholar, which covered information about the pathogenesis of BPD and the prospects for the use of MSCs in the treatment of newborns.&#x0D; Results. Over the past decades, the understanding of the pathogenesis of BPD has evolved from a complication of secondary lung damage after mechanical ventilation and the effect of increased oxygen concentration to a multifactorial disease in which prenatal and postnatal factors are involved. Adult stem cells have been found to be naturally capable of sustaining, generating and replacing terminally differentiated cells. Stem cells function in response to physiological cell turnover or tissue damage due to trauma caused by mechanical ventilation, barotrauma, volutrauma, and hyperoxia in preterm infants. It is believed that the therapeutic effect of MSCs is related to their immunomodulatory, anti-inflammatory, angiogenic, antibacterial and regenerative effects. According to ClinicalTrials.gov, out of 301 clinical studies devoted to BPD, 18 clinical studies are currently known to study the effectiveness of MSCs in the treatment of newborns with BPD, which have already involved 770 newborns. The largest number of studies is conducted in East Asian countries (5 in China, 5 in the Republic of Korea, and 2 in Taiwan).&#x0D; Conclusions. Currently, research into the clinical therapy of BPD with stem cells is mainly focused on umbilical cord blood MSCs, umbilical cord MSCs, and bone marrow MSCs. Success in proving the safety and feasibility of incorporating stem cells for BPD led to the appearance of the biological drug PNEUMOSTEM® – a product of allogeneic MSCs obtained from human umbilical cord blood.

UC-BSCs Exosomes Regulate Th17/Treg Balance in Patients with Systemic Lupus Erythematosus via miR-19b/KLF13.

Umbilical cord blood mesenchymal stem cells (UC-BSCs) are cells with low immunogenicity and differentiation potential, and the transfer of exosomes carried by UC-BSCs can regulate innate and adaptive immunity and affect immune homeostasis. This is an area of focus for autoimmune illnesses such as systemic lupus erythematosus (SLE). The target of this research was to investigate the immunomodulatory effect of exosomes produced from mesenchymal stem cells on SLE and its mechanism. After isolation of peripheral blood mononuclear cells (PBMC) from the SLE group and healthy group and treatment of SLE-derived PBMCs with UC-BSC-derived exosomes, the mRNA levels of corresponding factors in cells under different treatments were determined by RT-PCR, Th17/Treg content was analyzed by FCM (flow cytometry), and the targeted binding of microRNA-19b (miR-19b) to KLF13 was identified by in vitro experiments and bioinformatics analysis. The findings demonstrated that PBMC cells from SLE patients had higher proportions of Th17 subsets than the control group, whereas Treg subgroups with lower percentages were discovered. miR-19b's expression level was markedly reduced, which was inversely associated to the concentration of KLF13. In vitro experiments show that UC-BSC-derived exosome treatment can target KLF13 expression by increasing the miR-19b level, thereby regulating Th17/Treg balance and inhibiting the expression of inflammatory factors. According to the study's findings, SLE patients have dysregulated expression of the genes miR-19b and KLF13, and UC-BSC exosomes could regulate Th17/Treg cell balance and inflammatory factor expression in SLE patients through miR-19b/KLF13.

LC-MS/MS-based serum proteomics reveals a distinctive signature in a rheumatoid arthritis mouse model after treatment with mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are known to be able to modulate immune responses, possess tissue-protective properties, and exhibit healing capacities with therapeutic potential for various diseases. The ability of MSCs to secrete various cytokines and growth factors provides new insights into autoimmune-diseases such as rheumatoid arthritis (RA). RA is a systemic autoimmune disease that affects the lining of synovial joints, causing stiffness, pain, inflammation, and joint erosion. In recent years, MSCs-based therapies have been widely proposed as promising therapies in the treatment of RA. However, the mechanism involved in disease-specific therapeutic effects of MSCs on RA remains unclear. To clarify the mechanism involved in effects of MSCs on RA, proteomic profiling was performed using an RA mouse model before and after treatment with MSCs. In this study, treatment efficacy of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) was confirmed using a type II collagen-induced arthritis (CIA) mouse model. Results of measuring incidence rates of arthritis and clinical arthritis index (CAI) revealed that mice administrated with hUCB-MSCs had a significant reduction in arthritis severity. Proteins that might affect disease progression and therapeutic efficacy of hUCB-MSC were identified through LC-MS/MS analysis using serum samples. In addition, L-1000 analysis was performed for hUCB-MSC culture medium. To analysis data obtained from LC-MS/MS and L-1000, tools such as ExDEGA, MEV, and DAVID GO were used. Results showed that various factors secreted from hUCB-MSCs might play roles in therapeutic effects of MSCs on RA, with platelet activation possibly playing a pivotal role. Results of this study also suggest that SERPINE1 and THBS1 among substances secreted by hUCB-MSC might be key factors that can inhibit platelet activation. This paper is expected to improve our understanding of mechanisms involved in treatment effects of stem cells on rheumatoid arthritis.

Allogenic umbilical cord blood-mesenchymal stem cells are more effective than antibiotics in alleviating subclinical mastitis in dairy cows

Subclinical mastitis is an inflammatory disease that affects the milk production, fertility, and lifespan of animals, leading to significant losses to dairy industry. Antibiotics therapies are resulting in suboptimal benefits in treating subclinical mastitis due to prevalent antibiotic resistance in dairy herds. In a quest to develop alternative therapy, umbilical cord-derived mesenchymal stem cells (UCB-MSCs) and its extracellular vesicles (UCB-MSC-EVs) are used, in the present study, to validate its safety and efficacy as potential therapy for treatment of subclinical mastitis in dairy cows with respect to conventional antibiotic therapy (ABT). We isolated, in vitro cultured, and characterized the UCB-MSCs as well as UCB-MSC-EVs. The repeated infusions of low dose MSCs and EVs were delivered in healthy animals for safety analysis, followed by the same administrations in infected animals for therapeutic efficacy analysis. UCB-MSCs and UCB-MSC-EVs were found to be safe at 2 doses with 7-day gap of 5 × 107 cells/injection and EV equivalent to 500 μg protein in DPBS, respectively. Efficacy trials demonstrated significantly decreased somatic cell count to safe levels in milk samples of UCB-MSCs and UCB-MSC-EVs treated groups compared to antibiotic group. The leucocytes expression of anti-inflammatory cytokines, anti-microbial peptides, and angiogenic genes were significantly upregulated in UCB-MSCs and UCB-MSC-EVs treated groups as compared to antibiotic therapy group. Antibiotic therapy and UCB-MSC-EV groups failed to significantly decrease the gene expression of pro-inflammatory cytokine. In conclusion, the administration of UCB-MSCs and UCB-MSC-EVs through intravenous and local routes was found to be safe and efficacious for alleviating subclinical mastitis in dairy cows.

Conditioned medium derived from bovine umbilical mesenchymal stem cells as an alternative source of cell-free therapy.

Umbilical cord blood (UCB) cells are an important source of mesenchymal stem cells (MSCs). It is known that the umbilical cord is rich in hematopoietic stem cells, which influenced research on ontogeny and transplantation (allogeneic transplantation). In recent years, stem cell research has emerged as an area of major interest due to its prospective applications in various aspects of both human and veterinary medicine. Moreover, it is known that the application of MSCs has several weaknesses. The use of these cells has limitations in terms of tumorigenesis effect, delivery, safety, and variability of therapeutic response, which led to the use of secretomes as an alternative to cell-free therapy. The main obstacle in its use is the availability of human UCB as an origin of MSCs and MSCs’ secretomes, which are often difficult to obtain. Ethical issues regarding the use of stem cells based on human origin are another challenge, so an alternative is needed. Several studies have demonstrated that MSCs obtained from bovine umbilical cords have the same properties and express the same surface markers as MSCs obtained from human umbilical cords. Therefore, secretomes from MSCs derived from domestic animals (bovine) can possibly be used in human and veterinary medicine. This finding would contribute significantly to improve cell-free therapy. At present, the use of UCB MSCs derived from domestic animals, especially bovines, is very restricted, and only limited data about bovine UCB are available. Therefore, the aim of this review was to provide an updated overview of cell-free therapy and discuss the new possibilities introduced by the generation of this therapy derived from bovine umbilical MSCs as a promising tool in developing modern and efficient treatment strategies.

Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulate regenerative wound healing via transforming growth factor-\u03b2 receptor inhibition

BackgroundScar formation is a common consequence of skin wound healing, and no effective treatment exists. Umbilical cord blood mesenchymal stem cells (UCB-MSCs) can improve wound healing; however, the role of UCB-MSCs remains unclear and whether they can ameliorate scar formation has not been fully elucidated.MethodsTo determine the function of UCB-MSCs, we examined and compared the therapeutic effects of UCB-MSCs and UCB-MSC-derived exosomes (UCB-MSC-exo) on skin healing in rats. Moreover, UCB-MSC-exo-specific miRNAs were identified and their effects in inhibiting the human dermal fibroblast (HDF) differentiation into myofibroblasts were investigated.ResultsBoth UCB-MSCs and UCB-MSC-exo accelerated wound closure; reduced scar formation; improved the regeneration of skin appendages, nerves, and vessels; and regulated the natural distribution of collagen fibers in wound healing. Additionally, UCB-MSC-exo suppressed the excessive formation of myofibroblasts and collagen I and increased the proliferation and migration of skin cells in vivo and in vitro. Functional analysis showed that UCB-MSC-derived miRNAs were closely related to the transforming growth factor-β (TGF-β) signaling pathway, which could induce myofibroblast differentiation. We identified abundant miRNAs that were highly expressed in UCB-MSC-exo. miR-21-5p and miR-125b-5p were predicted to contribute to TGF-β receptor type II (TGFBR2) and TGF-β receptor type I (TGFBR1) inhibition, respectively. Using miRNA mimics, we found that miR-21-5p and miR-125b-5p were critical for anti-myofibroblast differentiation in the TGF-β1-induced HDF.ConclusionThe effect of UCB-MSCs in stimulating regenerative wound healing might be achieved through exosomes, which can be, in part, through miR-21-5p- and miR-125b-5p-mediated TGF-β receptor inhibition, suggesting that UCB-MSC-exo might represent a novel strategy to prevent scar formation during wound healing.

Systemic administration of mesenchymal stem cells loaded with a novel oncolytic adenovirus carrying IL-24/endostatin enhances glioma therapy.

Oncolytic adenovirus-mediated gene therapy shows promise for cancer treatment; however, the systemic delivery of oncolytic adenovirus to tumors remains challenging. Recently, mesenchymal stem cells (MSCs) have emerged as potential vehicles for improving delivery. Yet, because the oncolytic adenovirus replicates in MSCs, balancing MSC viability with viral load is key to achieving optimal therapeutic effect. We thus developed an all-in-one Tet-on system that can regulate replication of oncolytic adenovirus. Then, we loaded the novel oncolytic adenovirus carrying interleukin (IL)-24 and/or Endostatin in human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) for glioma therapy. In vitro assays demonstrated that this novel oncolytic adenovirus could efficiently replicate and kill glioma cells while sparing normal cells. Moreover, doxycycline effectively regulated oncolytic adenovirus replication in the hUCB-MSCs. The doxycycline induction group with dual expression of IL-24 and Endostatin exhibited significantly greater antitumor effects than other groups in a xenograft model of glioma. Thus, this strategy for systemic delivery of oncolytic adenovirus with its oncolytic activity controlled by a Tet-on system is a promising method for achieving antitumor efficacy in glioma, especially for metastatic tumors.

Umbilical cord tissue is a robust source for mesenchymal stem cells with enhanced myogenic differentiation potential compared to cord blood

Differentiation of mesenchymal stem cells (MSCs) derived from two different sources of fetal tissues such as umbilical cord blood (UCB) and tissue (UCT) into skeletal muscle have remained underexplored. Here, we present a comparative analysis of UCB and UCT MSCs, in terms of surface markers, proliferation and senescence marker expression. We find that CD45−CD34− MSCs obtained from UCT and UCB of term births display differences in the combinatorial expression of key MSC markers CD105 and CD90. Importantly, UCT MSCs display greater yield, higher purity, shorter culture time, and lower rates of senescence in culture compared to UCB MSCs. Using a robust myogenic differentiation protocol, we show that UCT MSCs differentiate more robustly into muscle than UCB MSCs by transcriptomic sequencing and specific myogenic markers. Functional assays reveal that CD90, and not CD105 expression promotes myogenic differentiation in MSCs and could explain the enhanced myogenic potential of UCT MSCs. These results suggest that in comparison to large volumes of UCB that are routinely used to obtain MSCs and with limited success, UCT is a more reliable, robust, and convenient source of MSCs to derive cells of the myogenic lineage for both therapeutic purposes and increasing our understanding of developmental processes.

Nanospheres Loaded with Curcumin Improve the Bioactivity of Umbilical Cord Blood-Mesenchymal Stem Cells via c-Src Activation During the Skin Wound Healing Process.

Curcumin, a hydrophobic polyphenol derived from turmeric, has been used a food additive and as a herbal medicine for the treatment of various diseases, but the clinical application of curcumin is restricted by its poor aqueous solubility and its low permeability and bioavailability levels. In the present study, we investigate the functional role of a nanosphere loaded with curcumin (CN) in the promotion of the motility of human mesenchymal stem cells (MSCs) during the skin wound healing process. CN significantly increased the motility of umbilical cord blood (UCB)-MSCs and showed 10,000-fold greater migration efficacy than curcumin. CN stimulated the phosphorylation of c-Src and protein kinase C which are responsible for the distinctive activation of the MAPKs. Interestingly, CN significantly induced the expression levels of α-actinin-1, profilin-1 and filamentous-actin, as regulated by the phosphorylation of nuclear factor-kappa B during its promotion of cell migration. In a mouse skin excisional wound model, we found that transplantation of UCB-MSCs pre-treated with CN enhanced wound closure, granulation, and re-epithelialization at mouse skin wound sites. These results indicate that CN is a functional agent that promotes the mobilization of UCB-MSCs for cutaneous wound repair.

The Effect of Intra-articular versus Intravenous Injection of Mesenchymal Stem Cells on Experimentally-Induced Knee Joint Osteoarthritis.

Background:Osteoarthritis (OA) is a chronic degenerative debilitating disease, primarily affects joints, particularly weight-bearing areas. The surface layer of the articular cartilage breaks down and wears away leading to rubbing of bones, pain, swelling, and joint stiffness.Aim and Objectives:This study investigates the possible therapeutic effects of intra-articular versus intravenous injection of umbilical cord blood mesenchymal stem cells (UCB-MSCs) against mono-iodoacetate-induced OA of the knee joints in male albino rats, using histological and immunohistochemical techniques.Materials and Methods:Thirty male adult albino rats were randomized into five groups as follows: Group (I) and (II): Served as control. Group (III): Osteoarthritic group. Group IV: Osteoarthritic and intraarticularly-injected MSCs. Group V: Osteoarthritic and intravenously-injected MSCs. Animals were sacrificed 1 month after stem cell injection, the right knee was prepared for histological techniques (Hematoxylin and Eosin and Toluidine blue stains) and immunohistochemical technique (Bax stain). Prussian blue stain was used to assess homing of MSCs in Groups IV and V.Results:Knee joint surface was irregular, fissured, and fragmented in Group III. In Groups IV and V, affected area was filled with newly formed tissue. Toluidine blue showed a decrease in matrix staining in Group III compared to both control and MSCs-treated groups. Chondrocytes in Group III showed strong Bax immunoreactivity and this reaction decreased in Group IV and V; however, Group V immunoreactivity was more than Group IV. Prussian blue stain showed labeled UCB-MSCs in many chondrocytes in Group IV and few chondrocytes in Group V.Conclusion:Intraarticularly-injected UCB-MSCs showed better healing of knee OA than intravenously-injected UCB-MSCs.

A 3-Dimensional Bioprinted Scaffold With Human Umbilical Cord Blood–Mesenchymal Stem Cells Improves Regeneration of Chronic Full-Thickness Rotator Cuff Tear in a Rabbit Model

Background: Chronic full-thickness rotator cuff tears (FTRCTs) represent a major clinical concern because they show highly compromised healing capacity. Purpose: To evaluate the efficacy of using a 3-dimensional (3D) bioprinted scaffold with human umbilical cord blood (hUCB)–mesenchymal stem cells (MSCs) for regeneration of chronic FTRCTs in a rabbit model. Study Design: Controlled laboratory study. Methods: A total of 32 rabbits were randomly assigned to 4 treatment groups (n = 8 per group) at 6 weeks after a 5-mm FTRCT was created on the supraspinatus tendon. Group 1 (G1-SAL) was transplanted with normal saline. Group 2 (G2-MSC) was transplanted with hUCB-MSCs (0.2 mL, 1 × 106) into FTRCTs. Group 3 (G3-3D) was transplanted with a 3D bioprinted construct without MSCs, and group 4 (G4-3D+MSC) was transplanted with a 3D bioprinted construct containing hUCB-MSCs (0.2 mL, 1 × 106 cells) into FTRCTs. All 32 rabbits were euthanized at 4 weeks after treatment. Examination of gross morphologic changes and histologic results was performed on all rabbits after sacrifice. Motion analysis was also performed before and after treatment. Results: In G4-3D+MSC, newly regenerated collagen type 1 fibers, walking distance, fast walking time, and mean walking speed were greater than those in G2-MSC based on histochemical and motion analyses. In addition, when compared with G3-3D, G4-3D+MSC showed more prominent regenerated tendon fibers and better parameters of motion analysis. However, there was no significant difference in gross tear size among G2-MSC, G3-3D, and G4-3D+MSC, although these groups showed significant decreases in tear size as compared with the control group (G1-SAL). Conclusion: Findings of this study show that a tissue engineering strategy based on a 3D bioprinted scaffold filled with hUCB-MSCs can improve the microenvironment for regenerative processes of FTRCT without any surgical repair. Clinical Relevance: In the case of rotator cuff tear, the cell loss of the external MSCs can be increased by exposure to synovial fluid. Therefore, a 3D bioprinted scaffold in combination with MSCs without surgical repair may be effective in increasing cell retention in FTRCT.

Current status of diagnosis and Mesenchymal stem cells therapy for acute pancreatitis.

Acute pancreatitis (AP) is an acute gastrointestinal disorder that is the most common and requiring emergency hospitalization. Its incidence is increasing worldwide, thus increasing the burden of medical services. Approximately 20% of the patients develop moderate to severe necrotizing pancreatitis associated with pancreatic or peri‐pancreatic tissue necrosis and multiple organ failure. There are many reports about the anti‐inflammatory effect of mesenchymal stem cells (MSCs) on pancreatitis and the repair of tissue damage. MSCs cells come from a wide range of sources, autologous MSCs come from bone marrow and allogeneic MSCs such as umbilical cord blood MSCs, placenta‐derived MSCs, etc. The wide source is not only an advantage of MSCs but also a disadvantage of MSCs. Because of different cell sources and different methods of collection and preparation, it is impossible to establish a unified standard method for evaluation of efficacy. The biggest advantage of iMSCs is that it can be prepared by a standardized process, and can be prepared on a large scale, which makes it easier to commercialize. This paper reviews the present status of diagnosis and progress of MSCs therapy for AP.

A Rabbit Model of Osteochondral Regeneration Using Three-Dimensional Printed Polycaprolactone-Hydroxyapatite Scaffolds Coated with Umbilical Cord Blood Mesenchymal Stem Cells and Chondrocytes.

BackgroundThis study aimed to investigate a rabbit model of osteochondral regeneration using three-dimensional (3-D) printed polycaprolactone-hydroxyapatite (PCL-HA) scaffolds coated with umbilical cord blood mesenchymal stem cells (UCB-MSCs) and chondrocytes.Material/MethodsNine female New Zealand white rabbits were included in the study. The 3-D PCL-HA scaffolds were prepared using fused deposition modeling 3-D printing technology. Seeding cells were prepared by co-culture of rabbit UCB-MSCs and chondrocytes with a ratio of 3: 1. A total of 4×106 cells were seeded on 3-D PCL-HA scaffolds and implanted into rabbits with femoral trochlear defects. After 8 weeks of in vivo implantation, 12 specimens were sampled and examined using histology and scanning electron microscopy (SEM). The International Cartilage Repair Society (ICRS) macroscopic scores and histological results were recorded and compared with those of the unseeded PCL-HA scaffolds.ResultsMean ICRS scores for the UCB-MSCs and chondrocyte-seeded PCL-HA scaffolds (group A) were significantly higher than the normal unseeded control (NC) PCL-HA scaffold group (group B) (P<0.05). Histology with safranin-O and fast-green staining showed that the UCB chondrocyte-seeded PCL-HA scaffolds significantly promoted bone and cartilage regeneration.ConclusionsIn a rabbit model of osteochondral regeneration using 3-D printed PCL-HA scaffolds, the UCB chondrocyte-seeded PCL-HA scaffold promoted articular cartilage repair when compared with the control or non-seeded PCL-HA scaffolds.

Umbilical Cord Blood Mesenchymal Stem Cells Enhance Lipopolysaccharide-Induced IL-10 and IL-37 Production in THP-1 Cells.

Umbilical cord blood mesenchymal stem cells (UCB-MSCs) have been shown to be a source of stem cells for use in cellular therapies and have immunomodulatory effects on several immune cells in an inflammatory environment. However, whether UCB-MSCs have immunomodulatory effects against lipopolysaccharide (LPS)-induced inflammatory cytokine secretion in macrophages and whether it is involved in phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway remain unclear. After co-culture of UCB-MSCs and phorbol 12-myristate 13-acetate (PMA)-activated human THP-1 cells using a transwell system, it showed that LPS significantly induced increases in the expression levels of interleukin 10 (IL-10), interleukin 37 (IL-37), phospho-PI3K (p-PI3K), and phospho-Akt (p-Akt) in macrophages. UCB-MSCs upregulated the expression of IL-10, IL-37, p-PI3K, and p-Akt, while it had no obvious effect on PI3K and Akt levels. Inhibitors of PI3K (LY294002) significantly suppressed the expression of IL-10, IL-37, p-PI3K, and p-Akt; however, it had no effect on the expression levels of PI3K and Akt. The present study demonstrated that UCB-MSCs increased the LPS-stimulated expression of IL-10 and IL-37 in macrophages through the PI3K/Akt signaling pathway.

Umbilical Cord Blood Mesenchymal Stem Cells as an Infertility Treatment for Chemotherapy Induced Premature Ovarian Insufficiency.

Background: Premature ovarian insufficiency (POI) is a challenging disease, with limited treatment options at the moment. Umbilical cord blood mesenchymal stem cells (UCMSCs) have demonstrated promising regenerative abilities in several diseases including POI. Materials and Method: A pre-clinical murine case versus vehicle control randomized study. Two experiments ran in parallel in each of the three groups. The first was to prove the ability of UCMSCs in restoring ovarian functions. The second was to prove improved fertility. A total of 36 mice were randomly assigned; 6 mice into each of 3 groups for two experiments. Group 1 (control), group 2 (sham chemotherapy), group 3 (stem cells). Results: In the first experiment, post-UCMSCs treatment (group 3) showed signs of restored ovarian function in the form of increased ovarian weight and estrogen-dependent organs (liver, uterus), increased follicular number, and a significant decrease in FSH serum levels (p < 0.05) compared to group 2, and anti-Mullerian hormone (AMH) serum levels increased (p < 0.05) in group 3 versus group 2. Immuno-histochemistry analysis demonstrated a higher expression of AMH, follicle stimulating hormone receptor (FSHR) and Inhibin A in the growing follicles of group 3 versus group 2. In the second experiment, post-UCMSCs treatment (group 3) pregnancy rates were higher than group 2, however, they were still lower than group 1. Conclusion: We demonstrated the ability of UCMSCs to restore fertility in female cancer survivors with POI and as another source of stem cells with therapeutic potentials.

Tropism of mesenchymal stem cell toward CD133+ stem cell of glioblastoma in vitro and promote tumor proliferation in vivo

BackgroundPrevious studies have demonstrated remarkable tropism of mesenchymal stem cells (MSCs) toward malignant gliomas, making these cells a potential vehicle for delivery of therapeutic agents to disseminated glioblastoma (GBM) cells. However, the potential contribution of MSCs to tumor progression is a matter of concern. It has been suggested that CD133+ GBM stem cells secrete a variety of chemokines, including monocytes chemoattractant protein-1 (MCP-1/CCL2) and stromal cell-derived factor-1(SDF-1/CXCL12), which could act in this tropism. However, the role in the modulation of this tropism of the subpopulation of CD133+ cells, which initiate GBM and the mechanisms underlying the tropism of MSCs to CD133+ GBM cells and their effects on tumor development, remains poorly defined.Methods/resultsWe found that isolated and cultured MSCs (human umbilical cord blood MSCs) express CCR2 and CXCR4, the respective receptors for MCP-1/CCL2 and SDF-1/CXCL12, and demonstrated, in vitro, that MCP-1/CCL2 and SDF-1/CXC12, secreted by CD133+ GBM cells from primary cell cultures, induce the migration of MSCs. In addition, we confirmed that after in vivo GBM tumor establishment, by stereotaxic implantation of the CD133+ GBM cells labeled with Qdots (705 nm), MSCs labeled with multimodal iron oxide nanoparticles (MION) conjugated to rhodamine-B (Rh-B) (MION-Rh), infused by caudal vein, were able to cross the blood-brain barrier of the animal and migrate to the tumor region. Evaluation GBM tumors histology showed that groups that received MSC demonstrated tumor development, glial invasiveness, and detection of a high number of cycling cells.ConclusionsTherefore, in this study, we validated the chemotactic effect of MCP-1/CCL2 and SDF-1/CXCL12 in mediating the migration of MSCs toward CD133+ GBM cells. However, we observed that, after infiltrating the tumor, MSCs promote tumor growth in vivo probably by release of exosomes. Thus, the use of these cells as a therapeutic carrier strategy to target GBM cells must be approached with caution.

Improved osteogenic differentiation of umbilical cord blood MSCs using custom made perfusion bioreactor

Background3D cell culture is an appropriate method to develop engineered bone tissue, where different bioreactors have been designed to mitigate the challenges in 3D culture. Currently, we tailored a perfusion reactor to witness human mesenchymal stem cells (MSCs) proliferation and differentiation over polylactic acid-polyethylene glycol (PLA/PEG) composite scaffolds. MethodsThe composite scaffolds with different weight ratios of PLA and PEG were prepared using solvent casting-particulate leaching technique. Human umbilcal card blood MSCs were cultured under dynamic and static conditions to elucidate the role of dynamic fluid flow in osteogenesis of MSCs. ResultsThe human MSCs distribution over the scaffolds was confirmed with fluorescent microscopy. Alkaline phosphatase (ALP), calcium mineralization, and collagen formation were found to be higher in PLA90 scaffolds than PLA100 and PLA75. PLA90 scaffolds with better cell adhesion/proliferartion were considered for bioreactor studies and they exhibited enhanced ALP, Ca+2 mineralization and collagen formation under dynamic perfusion than static culture. We further confirmed our observation by looking at expression levels of osteogenic marker (Runx2 and osteonectin) in differentiated MSCs subjected to perfusion culture compared to static culture. ConclusionThe results of the current investigation once again proves that dynamic perfusion cultures improve the osteogenic differentiation of MSCs over hybrid polymer scaffolds (PLA90) for effective bone regeneration.

Effects of fetal umbilical cord blood mesenchymal stem cells on γδT lymphocyte function and its related mechanism

Objective To explore the effects of fetal umbilical cord blood mesenchymal stem cells on γδT lymphocyte function and its related mechanism. Methods The Human peripheral blood mononuclear cells (PBMCs) or γδT cells were activated and expanded with 2 μg/ml pamidronate and 100 IU/ml interleukin-2 (IL-2) with or without the presence Fetal umbilical cord blood mesenchymal stem cells (UCMSCs). Flow cytometry was performed to evaluate the effects of UC-MSCs on proliferation, cytokine expression and cytotoxicity of γδT cells; besides, flow cytometry was used to detect the effects of UC-MSCs on Fas-L and TRAIL expression in γδT cells and γδT cell apoptosis as well. Results UC-MSCs inhibited γδT cell proliferation in a dose-dependent but cell-contact independent manner; when PBMCs and UC-MSCs were cultured at a ratio of 3∶1 and 40∶1, IFN-γ+ cells decreased by 46.7% and 31.4%, respectively (P=0.001, P=0.021), granzyme B positive cells increased by 79.7%, 165%, respectively, while the ratio of TNF-α and IL-10 positive cells did not change significantly compared with the control group (P=0.062); Cytotoxicity test results showed that, UCMSCs inhibited the cytotoxicity ofγδT cells against influenza virus H1N1 infected A549 cells, and when PBMCs and UC-MSCs were cultured at a ratio of 3∶1 and 40∶1, Fas-L+ γδT cells decreased by 87.6% and 37.5% (P=0.000, 0.009), the proportion of TRIAL+ γδT cells decreased by 43.2% and 18.7% (P=0.037, 0.042), however, UC-MSCs did not affect γδ T cell apoptosis (P=0.070, 0.064). Conclusion UC-MSCs can suppress γδT cells proliferation and cytotoxicity and modulated their cytokine production, and Fas-L and TRAIL were involved in the regulation. Key words: Umbilical cord blood mesenchymal stem cells; γ δ T cells; Proliferation; Cytokines; Apoptosis