Human umbilical cord-derived mesenchymal stem cell transplantation improves the long COVID.

No effective treatments can ameliorate symptoms of long COVID patients. Our study assessed the safety and efficacy of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) in the treatment of long COVID patients. Ten long COVID patients were enrolled and received intravenous infusions of UC-MSCs on Days 0, 7, and 14. Adverse events and clinical symptoms were recorded, and chest-high-resolution CT (HRCT) images and laboratory parameters were analyzed. During UC-MSCs treatment and follow-up, we did not observe serious adverse events, the symptoms of long COVID patients were significantly relieved in a short time, especially sleep difficulty, depression or anxiety, memory issues, and so forth, and the lung lesions were also repaired. The routine laboratory parameters did not exhibit any significant abnormalities following UC-MSCs transplantation (UMSCT). The proportion of regulatory T cells gradually increased, but it was not statistically significant until 12 months. The proportion of naive B cells was elevated, while memory B cells, class-switched B-cells, and nonswitched B-cells decreased at 1 month after infusion. Additionally, we observed a transient elevation in circulating interleukin (IL)-6 after UMSCT, while tumor necrosis factor (TNF)-α, IL-17A, and IL-10 showed no significant changes. The levels of circulating immunoglobulin (Ig) M increased significantly at month 2, while IgA increased significantly at month 6. Furthermore, the SARS-CoV-2 IgG levels remained consistently high in all patients at Month 6, and there was no significant decrease during the subsequent 12-month follow-up. UMSCT was safe and tolerable in long COVID patients. It showed potential in alleviating long COVID symptoms and improving interstitial lung lesions.

[Optimization of chromosome flaking technique for mesenchymal stem cells].

OBJECTIVE: To optimize the condition for chromosome flaking of mesenchymal stem cells to ensure the cytogenetic quality control of expanding production and clinical application. METHODS: Chromosomal flaking methods were optimized from current chromosome preparation techniques from the aspects of MSCs cell culture concentration, colchicine treatment time and low permeability time. RESULTS: By repeated pre-experiments, the optimal MSCS chromosome flaking condition of MSCs was determined as cell culture concentration of (1-2)× 106 cells per T25 cell culture bottle, and the colchicines processing time was determined as 2 hours and 10 minutes, and the low permeability was 1 hour. CONCLUSION: The optimized chromosome flaking condition can fulfill the requirement of cytogenetic quality control for MSCs.

[Angiogenic ability of 3 different tissues-derived mesenchymal stem cells on endothelial progenitor cells].

OBJECTIVE: To compare the ability between bone marrow-derived mesenchymal stem cells (MSCs) (BM-MSCs) and adipose-derived MSCs (AD-MSCs) or umbilical cord-derived MSCs (UC-MSCs) on promotion of vessels formation and vessels stabilization relevant to the functions of EPCs.
 Methods: In vitro, co-culture blood vessel test was performed to compare the angiogenic ability between BM-MSCs, AD-MSCs or UC-MSCs. In vivo, angiogenic assay dependent on basement membrane matrix Matrigel and immunohistochemistry were performed to compare the ability of vessels formation functions between BM-MSCs and AD-MSCs or UC-MSCs.
 Results: The lengths and dots of vascular structures formed by EPCs on AD-MSCs layer are greater than those by EPCs on BM-MSCs layer and UC-MSCs layer in angiogenic assay in vitro. The stability of the capillary-like structures formed by EPCs with AD-MSCs on Matrigel was more stable than that by the BM-MSCs, UC-MSCs or EPCs. AD-MSCs and EPCs could form abundant functional vessels with blood perfusion in Matrigelin vivo; UC-MSCs and EPCs could form a few functional vessels with blood perfusion in Matrigelin vivo; BM-MSCs and EPCs could form broken vessels with hemocytes leakage in Matrigel in vivo.
 Conclusion: AD-MSCs have the stronger ability to promote the angiogenesis and stabilize the vessels compared with BM-MSCs or UC-MSCs ex vivo and in vivo.

[Therapeutic potential of BMSCs for premature ovarian failure in mice].

OBJECTIVE: To explore the therapeutic effects of bone marrow-derived mesenchymal stem cells (BMSCs) on premature ovarian failure (POF) in mice induced by cyclophosphamide (CTX) and the possible mechanisms.
 Methods: Mouse BMSCs were identified through detection of cell surface markers by flow cytometry. The model of mouse POF was induced by intraperitoneal injection of CTX at a dose of 50 mg/kg, once daily for 15 days. BMSCs were transplanted into POF mice at 2×106 cells/mouse by tail veil. The ovarian tissues were collected for HE staining at 7 days after transplantation to observe the changes of ovarian structure and real-time PCR was performed to detect the folliculogenesis gene expression.
 Results: BMSCs showed positive expression of CD29 and CD90 while low expression for endothelial and hematopoietic cell markers CD31 and CD34. The numbers of primodial follicle, primary follicle, secondary follicle and antral follicle were significantly decreased, but the numbers of atretic follicle were significantly increased in CTX induced-POF mice (P<0.05). BMSCs transplantation effectively repaired the structure of damaged ovary. The significant reduction of atretic follicle and significant increase of antral follicle and secondary follicle were observed in ovaries of BMSCs-treated mouse(P<0.05). BMSCs-transplanted mouse ovaries showed the increased mRNA expression levels of Nano3, Nobox, and Lhx8 (P<0.05).
 Conclusion: BMSCs could effectively repair ovarian structure and promote follicle development in CTX-induced POF mouse.

The therapeutic effect of anti-CD19 antibody on DHEA-induced PCOS mice.

Immune dysregulation has been summarized as a critical factor in the occurrence and development of Polycystic ovary syndrome (PCOS), but potential mediators and mechanisms remain unclear. Our previous study showed that CD19+ B cells were involved in the pathogenesis of dehydroepiandrosterone (DHEA)-induced PCOS mice. Here, we studied the therapeutic potential of anti-CD19 antibody (aCD19 Ab) on DHEA-induced PCOS mice. The results showed that aCD19 Ab treatment improved ovarian pathological structure and function of PCOS mice, manifested by an increased number of corpus luteum, a decreased number of cystic follicles and atretic follicles, and regular estrus cycles. The aCD19 Ab treatment reduced the proportion of splenic CD21+ CD23low marginal zone B cells as well as the level of serum IgM and decreased the percentage of peripheral blood and splenic neutrophils. In particular, aCD19 Ab treatment reduced the apoptosis of granulosa cells and macrophage infiltration in ovarian secondary follicles of PCOS mice, as well as the expression of TNF-α in ovarian tissue and serum TNF-α levels. Moreover, we confirmed that TNF-α induced the apoptosis of human ovarian granulosa tumor cell line cells in vitro. Thus, our work demonstrates that aCD19 Ab treatment improves ovarian pathological phenotype and function by reducing local and systemic inflammation in PCOS mice, which may provide a novel insight into PCOS therapy.

Expert Consensus on the Application of Stem Cells in Psoriasis Research and Clinical Trials.

Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.

Co-transplantation of mesenchymal stromal cells and cord blood cells in treatment of diabetes.

BACKGROUND AIMS: Stem cells provide a promising source for treatment of type 1 diabetes, but the treatment strategy and mechanism remain unclear. The aims of this study were to investigate whether co-transplantation of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) and cord blood mononuclear cells (CB-MNCs) could reverse hyperglycemia in type 1 diabetic mice and to determine the appropriate ratio for co-transplantation. The treatment mechanism was also studied. METHODS: A simple and efficient isolation method was developed to generate qualified UC-MSCs. UC-MSCs and CB-MNCs were then transplanted into type 1 diabetic mice at different ratios (UC-MSCs to CB-MNCs = 1:1, 1:4, 1:10) to observe the change in blood glucose concentration. Histology, immunohistochemistry, and human Alu polymerase chain reaction assay were performed to evaluate for the presence of donor-derived cells and the repair of endogenous islets. We also induced UC-MSCs into islet-like cells under specific culture conditions to determine their differentiate potential in vitro. RESULTS: Co-transplantation of UC-MSCs and CB-MNCs at a ratio of 1:4 effectively reversed hyperglycemia in diabetic mice. The detection of human Alu sequence indicated that the engraftment of donor-derived cells had homed into the recipient's pancreas and kidney. Although neither human insulin nor human nuclei antigen was detected in the regenerated pancreas, UC-MSCs could differentiate into insulin-secreted cells in vitro. CONCLUSIONS: Co-transplantation of UC-MSCs and CB-MNCs at a ratio of 1:4 could efficiently reverse hyperglycemia and repair pancreatic tissue.

Characterization and comparison of embryonic stem cell-derived KDR+ cells with endothelial cells.

Growing interest in utilizing endothelial cells (ECs) for therapeutic purposes has led to the exploration of human embryonic stem cells (hESCs) as a potential source for endothelial progenitors. In this study, ECs were induced from hESC lines and their biological characteristics were analyzed and compared with both cord blood endothelial progenitor cells (CBEPCs) and human umbilical vein endothelial cells (HUVECs) in vitro. The results showed that isolated embryonic KDR+ cells (EC-KDR+) display characteristics that were similar to CBEPCs and HUVECs. EC-KDR+, CBEPCs and HUVECs all expressed CD31 and CD144, incorporated DiI-Ac-LDL, bound UEA1 lectin, and were able to form tube-like structures on Matrigel. Compared with CBEPCs and HUVECs, the expression level of endothelial progenitor cell markers such as CD133 and KDR in EC-KDR+ was significantly higher, while the mature endothelial marker vWF was lowly expressed in EC-KDR+. In summary, the study showed that EC-KDR+ are primitive endothelial-like progenitors and might be a potential source for therapeutic vascular regeneration and tissue engineering.

Metformin abrogates pathological TNF-α-producing B cells through mTOR-dependent metabolic reprogramming in polycystic ovary syndrome.

B cells contribute to the pathogenesis of polycystic ovary syndrome (PCOS). Clinically, metformin is used to treat PCOS, but it is unclear whether metformin exerts its therapeutic effect by regulating B cells. Here, we showed that the expression level of tumor necrosis factor-alpha (TNF-α) in peripheral blood B cells from PCOS patients was increased. Metformin used in vitro and in vivo was able to reduce the production of TNF-α in B cells from PCOS patients. Administration of metformin improved mouse PCOS phenotypes induced by dehydroepiandrosterone (DHEA) and also inhibited TNF-α expression in splenic B cells. Furthermore, metformin induced metabolic reprogramming of B cells in PCOS patients, including the alteration in mitochondrial morphology, the decrease in mitochondrial membrane potential, Reactive Oxygen Species (ROS) production and glucose uptake. In DHEA-induced mouse PCOS model, metformin altered metabolic intermediates in splenic B cells. Moreover, the inhibition of TNF-α expression and metabolic reprogramming in B cells of PCOS patients and mouse model by metformin were associated with decreased mTOR phosphorylation. Together, TNF-α-producing B cells are involved in the pathogenesis of PCOS, and metformin inhibits mTOR phosphorylation and affects metabolic reprogramming, thereby inhibiting TNF-α expression in B cells, which may be a new mechanism of metformin in the treatment of PCOS.

Blood CD4+CD25+ T regulatory cells constitute a potential predictive marker of subsequent miscarriage in unexplained recurrent pregnancy loss.

The aim of this study was to investigate the relationship between pre-pregnancy blood immune status and unexplained recurrent pregnancy loss (URPL), and to evaluate the predictive value of pre-pregnancy blood Treg levels for subsequent miscarriage in patients with URPL. We retrospectively analyzed 76 women who had experienced two or more miscarriages before 24 weeks of gestation for no obvious reason, and 74 women who had achieved live births as controls. Flow-cytometric analysis of peripheral blood CD4 + T cells, CD8 + T cells, NK cells, NKT cells, B cells, NK cell subpopulations (including CD56bright NK cells, CD56dim NK cells, CD56dimCD16+ NK cells, and CD56brightCD16- NK cells) was executed in the luteal phase of women in the URPL and control groups. When we reviewed and analyzed reproductive outcomes in URPL patients, we found that blood Tregs were significantly lower in the URPL group than in the controls (1.89% ± 0.61% vs. 2.15% ± 0.58%, P < 0.01) during the luteal phase pre-pregnancy. However, we discerned no differences among blood CD4+T cells, CD8+T cells, B cells, NKT cells, or NK cells, NK subpopulations (CD56bright NKs, CD56dim NKs, CD56dimCD16+ NKs, or CD56brightCD16- NKs) between the two groups. By implementing receiver operating characteristic (ROC) curve analysis to determine whether Treg levels predicted subsequent miscarriages, we found that the area under the ROC curves was 0.714, and that the cutoff value was 1.35, with a sensitivity of 0.556 and specificity of 0.923. Based on the cutoff value, we divided pregnant URPL patients into two groups, demonstrating that the subsequent miscarriage rates in the low-Treg level group (<1.35%) were significantly higher than those in the normal-Treg level group (>1.35%) (71.43% vs. 14.29%, P < 0.01). CONCLUSION: The pre-pregnancy blood Treg level was a potential marker that predicted subsequent miscarriage in women with URPL.

Human umbilical cord mesenchymal stem cells for psoriasis: a phase 1/2a, single-arm study.

Psoriasis is a common, chronic immune-mediated systemic disease that had no effective and durable treatment. Mesenchymal stem cells (MSCs) have immunomodulatory properties. Therefore, we performed a phase 1/2a, single-arm clinical trial to evaluate the safety and efficacy of human umbilical cord-derived MSCs (UMSCs) in the treatment of psoriasis and to preliminarily explore the possible mechanisms. Seventeen patients with psoriasis were enrolled and received UMSC infusions. Adverse events, laboratory parameters, PASI, and PGA were analyzed. We did not observe obvious side effects during the treatment and 6-month follow-up. A total of 47.1% (8/17) of the psoriasis patients had at least 40% improvement in the PASI score, and 17.6% (3/17) had no sign of disease or minimal disease based on the PGA score. And the efficiency was 25% (2/8) for males and 66.7% (6/9) for females. After UMSC transplantation (UMSCT), the frequencies of Tregs and CD4+ memory T cells were significantly increased, and the frequencies of T helper (Th) 17 and CD4+ naive T cells were significantly decreased in peripheral blood (PB) of psoriasis patients. And all responders showed significant increases in Tregs and CD4+ memory T cells, and significant decreases in Th17 cells and serum IL-17 level after UMSCT. And baseline level of Tregs in responders were significantly lower than those in nonresponders. In conclusion, allogeneic UMSCT is safe and partially effective in psoriasis patients, and level of Tregs may be used as a potent biomarker to predict the clinical efficacy of UMSCT. Trial registration Clinical Trials NCT03765957.

Case Report: Human Umbilical Cord Mesenchymal Stem Cells as a Therapeutic Intervention for a Critically Ill COVID-19 Patient.

Here we report a critically ill patient who was cured of SARS-CoV-2 infection in Changsha, China. A 66-year-old Chinese woman, with no significant past medical history, developed severe pneumonia-like symptoms and later diagnosed as severe COVID-19 pneumonia. Within 2 months of hospitalization, the patient deteriorated to ARDS including pulmonary edema and SIRS with septic shock. When treatment schemes such as antibiotics plus corticosteroids showed diminished therapeutic value, hUCMSC therapy was compassionately prescribed under the patient's consent of participation. After treatment, there was significant improvement in disease inflammation-related indicators such as IL-4, IL-6, and IL-10. Eventually, it confirmed the therapeutic value that hUCMSCs could dampen the cytokine storm in the critically ill COVID-19 patient and modulated the NK cells. In the continued hUCMSC treatment, gratifying results were achieved in the follow-up of the patient. The data we acquired anticipate a significant therapeutic value of MSC treatment in severe and critically ill patients with COVID-19, while further studies are needed.

Umbilical Cord Mesenchymal Stem Cells for Inhibiting the Fibrosis and Autoimmune Development in HOCl-Induced Systemic Scleroderma Mouse Model.

BACKGROUND AND OBJECTIVES: Systemic scleroderma (SSc) is a rare and serious connective tissue disease, an autoimmune disease, and a rare refractory disease. In this study, preventive effect of single systemic human umbilical cord mesenchymal stem cells (UC-MSCs) transfusion on SSc was preliminarily explored. METHODS AND RESULTS: SSc mouse model was established by daily intradermal injection of Hypochlorite (HOCl). SSc mice were treated by single transfusion of UC-MSCs at 0.625×105, 2.5×105 and 1×106 respectively. At the 42nd day of intradermal injection of HOCl, the symptoms showed up by skin and alveolar wall thickening, lymphocytic infiltration, increased collagen in skin/lung, and the increased proportion of CD3＋CD4＋CD25＋FoxP3＋ cells (a Treg subset) in spleen. After UC-MSCs transfusion, the degree of skin thickening, alveolar wall thickening and lymphocyte infiltration were decreased, the collagen sedimentation in skin/lung was decreased, and the proportion of CD3＋CD4＋CD25＋ FoxP3＋ cells was decreased. CONCLUSIONS: UC-MSC can achieve a preventive effect in SSc mice by fibrosis attenuation and immunoregulation.

SPARC promotes insulin secretion through down-regulation of RGS4 protein in pancreatic ß cells.

SPARC-deficient mice have been shown to exhibit impaired glucose tolerance and insulin secretion, but the underlying mechanism remains unknown. Here, we showed that SPARC enhanced the promoting effect of Muscarinic receptor agonist oxotremorine-M on insulin secretion in cultured mouse islets. Overexpression of SPARC down-regulated RGS4, a negative regulator of ß-cell M3 muscarinic receptors. Conversely, knockdown of SPARC up-regulated RGS4 in Min6 cells. RGS4 was up-regulated in islets from sparc -/- mice, which correlated with decreased glucose-stimulated insulin secretion (GSIS). Furthermore, inhibition of RGS4 restored GSIS in the islets from sparc -/- mice, and knockdown of RGS4 partially decreased the promoting effect of SPARC on oxotremorine-M-stimulated insulin secretion. Phosphoinositide 3-kinase (PI3K) inhibitor LY-294002 abolished SPARC-induced down-regulation of RGS4. Taken together, our data revealed that SPARC promoted GSIS by inhibiting RGS4 in pancreatic ß cells.

Effects of an endothelial cell-conditioned medium on the hematopoietic and endothelial differentiation of embryonic stem cells.

We have examined the effect of mouse bone marrow endothelial cell-conditioned medium (mEC-CM) on hematopoietic and endothelial differentiation of mouse embryonic stem cells (mESCs). mEC-CM can efficiently promote the differentiation of mESCs into Flk(+) cells and hematopoietic colony-forming cells. mEC-CM proved to be as potent as a cytokine cocktail comprised of VEGF, bFGF, IGF and EGF. After inducing mESCs with mEC-CM, cobblestone-like cells were mechanically selected and identified which had the ability to incorporate DiI-Ac-LDL. DiI-Ac-LDL-positive cells were endothelial-like cells due to their expression of CD31 and Flk1, ability to bind to UEA1 and capacity to form capillary-like tube structures on matrigel. In conclusion, mEC-CM can efficiently promote the differentiation of mESCs into endothelial cells and hematopoietic colony-forming cells. The differentiated endothelial-like cells can be isolated by using DiI-Ac-LDL labeling and mechanical selection.

Effect of oxidized low-density lipoprotein on survival and function of endothelial progenitor cell mediated by p38 signal pathway.

This study was designed to investigate whether oxidized low-density lipoprotein (oxLDL) affects the survival and activity of endothelial progenitor cell (EPC) mediated by p38 mitogen-activated protein kinase (MAPK). EPCs were isolated from human peripheral blood in endothelial cell growth medium-2. Incubation with oxLDL at 100 microg/mL decreased EPC number. Treated with oxLDL resulted in increase of EPC apoptosis and in decrease of EPC proliferation. Treatment with oxLDL resulted in a significantly reduced migratory rate of EPCs and reduced adhesion to fibronectin. Treatment with oxLDL impaired the in vitro angiogenesis ability of EPCs. However, all the detrimental effects on EPC were attenuated by pretreatment of EPCs with SB203580, an inhibitor of the p38 MAPK. In addition, the inhibition of the p38-kinase by SB203580 also significantly improved basal number and functions of EPCs. Western blot analysis revealed that oxLDL induced dose- and time-dependent activation of the p38 MAPK. These results demonstrated that p38 MAPK plays a critical role in regulating the number and functions of EPCs in vitro. SB203580 can improve the number and functions of EPCs under basal conditions and prevent the negative effects of oxLDL on the number and functions of EPCs and may be useful to improve the number and function of EPCs for potential cell therapy.

Suicide Gene Therapy Against Malignant Gliomas by the Local Delivery of Genetically Engineered Umbilical Cord Mesenchymal Stem Cells as Cellular Vehicles.

BACKGROUND: Glioblastoma (GBM) is a malignant tumor that is difficult to eliminate, and new therapies are thus strongly desired. Mesenchymal stem cells (MSCs) have the ability to locate to injured tissues, inflammation sites and tumors and are thus good candidates for carrying antitumor genes for the treatment of tumors. Treating GBM with MSCs that have been transduced with the herpes simplex virus thymidine kinase (HSV-TK) gene has brought significant advances because MSCs can exert a bystander effect on tumor cells upon treatment with the prodrug ganciclovir (GCV). OBJECTIVE: In this study, we aimed to determine whether HSV-TK-expressing umbilical cord mesenchymal stem cells (MSCTKs) together with prodrug GCV treatment could exert a bystander killing effect on GBM. METHODS AND RESULTS: Compared with MSCTK: U87 ratio at 1:10,1:100 and 1:100, GCV concentration at 2.5µM or 250µM, when MSCTKs were cocultured with U87 cells at a ratio of 1:1, 25 µM GCV exerted a more stable killing effect. Higher amounts of MSCTKs cocultured with U87 cells were correlated with a better bystander effect exerted by the MSCTK/GCV system. We built U87-driven subcutaneous tumor models and brain intracranial tumor models to evaluate the efficiency of the MSCTK/GCV system on subcutaneous and intracranial tumors and found that MSCTK/GCV was effective in both models. The ratio of MSCTKs and tumor cells played a critical role in this therapeutic effect, with a higher MSCTK/U87 ratio exerting a better effect. CONCLUSION: This research suggested that the MSCTK/GCV system exerts a strong bystander effect on GBM tumor cells, and this system may be a promising assistant method for GBM postoperative therapy.

Effects of human umbilical cord blood CD34+ cell transplantation in neonatal hypoxic-ischemia rat model.

Perinatal brain injury can cause death in the neonatal period and lifelong neurodevelopmental deficits. Stem cell transplantation had been proved to be effective approach to ameliorate neurological deficits after brain damage. In this study we examine the effect of human umbilical cord blood CD34+ cells on model of neonatal rat hypoxic-ischemic brain damage and compared the neuroprotection of transplantation of CD34+ cells to mononuclear cells from which CD34+ cells isolated on neonatal hypoxic-ischemia rat model. Seven-day-old Sprague-Dawley rats were subjected to hypoxic-ischemic (HI) injury, CD34+ cells (1.5 × 104 cells) or mononuclear cells (1.0 × 106 cells) were transplanted into mice by tail vein on the 7 day after HI. The transplantation of CD34+ cells significantly improved motor function of rat, and reduced cerebral atrophy, inhibited the expression of glial fibrillary acidic protein (GFAP) and apoptosis-related genes: TNF-α, TNFR1, TNFR2, CD40, Fas, and decreased the activation of Nuclear factor kappa B (NF-κB) in damaged brain. CD34+ cells treatment increased the expression of DCX and lectin in ipsilateral brain. Moreover, the transplantation of CD34+ cells and MNCs which were obtained from the same amount of human umbilical cord blood had similar effects on HI. Our data demonstrated that transplantation of human umbilical cord blood CD34+ cells can ameliorate the neural functional defect and reduce apoptosis and promote nerve and vascular regeneration in rat brain after HI injury and the effects of transplantation of CD34+ cells were comparable to that of MNCs in neonatal hypoxic-ischemia rat model.

Mesenchymal Stem Cells Alleviate Moderate-to-Severe Psoriasis by Reducing the Production of Type I Interferon (IFN-I) by Plasmacytoid Dendritic Cells (pDCs).

The anti-inflammatory and immunomodulatory properties of mesenchymal stem cells (MSCs) have been proposed to be involved in some autoimmune diseases and have been successfully tested in patients and mice. But their contribution to psoriasis and the underlying mechanisms involved remains elusive. Here, we explored the feasibility of using human umbilical cord-derived MSC (hUC-MSC) infusion as a therapeutic approach in an imiquimod- (IMQ-) induced psoriasis mouse model. MSC infusion were found to significantly reduce the severity and development of psoriasis, inhibit the infiltration of immune cells to the skin, and downregulate the expression of several proinflammatory cytokines and chemokines. Our results provide an explanation for the therapeutic effects of MSC infusion by first suppressing neutrophil function and then downregulating the production of type I interferon (IFN-I) by plasmacytoid dendritic cells (pDCs). Therefore, we discovered a novel mechanism of stem cell therapy for psoriasis. In summary, our results showed that MSC infusion could be an effective and safe treatment for psoriasis.