A Life-Threatening Complication During the Fourth Pregnancy Due to Acute Promyelocytic Leukemia: A Case Report.

Incidents of leukemia in pregnancy are infrequent with only one case found from 75,000 to 100,000 pregnancies. The pathophysiological mechanism of leukemia during pregnancy is still unclear. Leukemia which occurs in pregnancy is usually acute and predominantly the myeloid type.A 35-year-old woman in her fourth pregnancy with a gestational age of 38-39 weeks, came to the emergency department (ED) with complaints of contractions since 4.5 hours before admission. The contraction was not accompanied by discharge, mucus, or blood, and fetal movements was still active. She denied complaints of fever, nausea, vomiting, dizziness, shortness of breath, weakness, fatigue, lethargy, and bleeding. Physical examination results, both palpebral conjunctiva were pale. Laboratory examination results of a complete blood count, white blood cell count were 2,930/uL, hemoglobin 8.3 g/dL, Hct 24.10%, erythrocytes 2.78x106/µL, platelets 62,000/µL. Bone Marrow Aspiration (BMA) revealed Acute Promyelocytic Leukemia (APL).APL is a subtype of Acute Myelogenous Leukemia (AML). Persistent fatigue, recurrent infections, and bleeding are common manifestations of APL. The diagnosis of APL is made by bone marrow aspiration examination, and it is safe for pregnancy. APL therapy in pregnancy uses All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (ATO). ATRA and ATO are highly teratogenic, but recent studies have reported no fetal abnormalities.Accuracy and speed in diagnosing and initiating APL therapy in pregnancy are essential in preventing serious complications.

Ameliorating Effect of Apium graveolens (Celery) Extracts on IL-6 Plasma Level and Expression of Caspase 3 on Liver in Animal Model of Lead Intoxication.

<b>Background and Objective:</b> Lead poisoning (Pb) is a big problem because it is found in almost all objects in daily life such as vehicle fuel, water pipes, ceramics, cosmetics and others. Continuous lead exposure can increase ROS resulting in an increase in hepatic IL-6 and caspase 3 which replaces hepatic cell apoptosis. The objective of this study was to determine the effect of <i>Apium graveolens</i> (celery) extract on plasma IL-6 and hepatic caspase 3 levels. <b>Materials and Methods:</b> This study used a post-test control group design. The research subjects were 20 Wistar rats that met the inclusion criteria and were divided into 4 groups randomly, namely (a) Sham group that had no treatment, (b) Negative control group was induced with lead acetate 200 mg kg¹ body weight/day without any treatment (c) Positive control group and (d) Treated group. On the 15th day, blood was taken to check IL-6 levels and tissue was taken for liver caspase 3 examination by immunohistochemical method. Data analysis used the one-way ANOVA test and continued with the <i>post hoc</i> LSD test. <b>Results:</b> The highest mean caspase 3 expression was in the control group 45.84±4.39 pg mL¹, while the mean of IL-6 plasma level was highest in the P1 641.33±39.72 pg mL¹ group. The Mann-Whitney test showed a significant difference in IL-6 levels between the study groups (p = 0.000). The Mann-Whitney test showed a significant difference in caspase 3 levels between the study groups (p = 0.000). <b>Conclusion:</b> Giving celery extract 300 mg kg¹ body weight/day affects plasma IL-6 and hepatic caspase 3 levels in lead acetate-induced rats.

Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Promotes Liver Regeneration and Anti-Fibrotic Effect in Liver Fibrosis Animal Model.

<b>Background and Objective:</b> Liver fibrosis (LF) is a most common pathological process characterized by the activation of hepatocytes leading to the accumulation of extracellular matrix (ECM). Hypoxia precondition treated in MSCs (H-MSCs) could enhance their immunomodulatory and regeneration capability, through expressing robust anti-inflammatory cytokines and growth factors, known as H-MSCs secretome (SH-MSCs) that are critical for the improvement of liver fibrosis. However, the study regarding the efficacy and mechanism of action of SH-MSCs in ameliorating liver fibrosis is still inconclusive. In this study, the therapeutic potential and underlying mechanism for SH-MSCs in the treatment of liver fibrosis were investigated. <b>Materials and Methods:</b> A rat model with liver fibrosis induced by CCl₄ was created and maintained for 8 weeks. The rats received intravenous doses of SH-MSCs and secretome derived from normoxia MSCs (SN-MSCs), filtered using a tangential flow filtration (TFF) system with different molecular weight cut-off categories, both at a dosage of 0.5 mL. The ELISA assay was employed to examine the cytokines and growth factors present in both SH-MSCs and SN-MSCs. On the ninth day, the rats were euthanized and liver tissues were collected for subsequent histological examination and analysis of mRNA expression. <b>Results:</b> The ELISA test revealed that SH-MSCs exhibited higher levels of VEGF, PDGF, bFGF, IL-10, TGF-ß and IL-6 compared to SN-MSCs. <i>In vivo</i>, administration of SH-MSCs notably decreased mortality rates. It also demonstrated a reduction in liver fibrosis, collagen fiber areas, α-SMA positive staining and relative mRNA expression of TGF-ß. Conversely, SN-MSCs also contributed to liver fibrosis improvement, although SH-MSCs demonstrated more favorable outcomes. <b>Conclusion:</b> Current findings suggested that SH-MSCs could improve CCl₄-induced liver fibrosis and decrease α-SMA and TGF-ß expression.

Hypoxic mesenchymal stem cells (MSCS)-induced interleukin (IL)-10 alleviate systemic lupus erythematosus (SLE) infl ammation through inhibiting interferon (IFN)-gamma production.

Aim To determine the eff ect of hypoxic mesenchymal stem cells (MSCs) on the interleukin (IL)-10 and interferon (IFN)-gamma in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients. Methods This study used a post-test control group design. Hypoxic MSCs were isolated and characterized according to their surface marker expression and diff erentiation capacities. PBMCs isolated from SLE patients were divided into three groups: control and two treatment groups. The treatment groups were treated by co-culturing MSCs to PBMCs with a ratio of 1:10 (T1) and 1:1 (T2) for 48 h incubation. Furthermore, IFN-gamma and IL-10 levels were determined by cytometric bead array (CBA) fl ow cytometry. Results Hypoxic MSCs signifi cantly decreased the IFN-gamma levels and increased the IL-10 levels in dose-dependent manner compared to the control group. The highest activity of hypoxic MSCs was noticed in T2 group. Conclusion Hypoxic MSCs- induced IL-10 are important in the control of anti-infl ammatory eff ect on SLE through inhibiting IFN-gamma.

Combination Effect of Rotator Cuff Repair with Secretome-hypoxia MSCs Ameliorates TNMD, RUNX2, and Healing Histology Score in Rotator Cuff Tear Rats.

Objectives: In order to treat a rat model of rotator cuff rupture, this work concentrated on the expression of TNMD and RUNX2, followed by rotator cuff repair and secretome-hMSCs. Methods: A total of thirty 10-weeks-old male Sprague-Dawley rats were separated into five groups randomly, RC on week 0, lesion treated with a rotator cuff repair and saline (RC + NaCl group, n = 6) for 2 and 8 weeks, and lesion treated with a rotator cuff repair and secretome-hMSCs (RC + secretome-hMSC group, n = 6) for 2 and 8 weeks. The supraspinatus and infraspinatus muscle-tendon units were obtained for histological and biomechanical investigation at 0, 2 and 8 weeks following injury. Results: The findings showed that, in comparison with the RC + NaCl group, secretome-hMSCs significantly improved tendon repair by upregulating TNMD and RUNX2 expression and histology score. Conclusion: Combining Secretome-hypoxia MSCs with RC healing may help rats with rotator cuff tears.

The Effect of Secreted IL-10 from Mesenchymal Stem Cell on Immune Checkpoint Molecules.

Background: Immunosuppression in sepsis is hypothesized to result from the increased expression of the immune checkpoint molecules programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1). PD-1 and PD-L1 blockade therapies have been reported to increase survival in septic animals. Currently, the interleukin (IL)-10 within mesenchymal stem cell (MSC) secretome is known for its immunomodulatory capacity. Objective: To study the effect of IL-10 within MSC secretome on the expression of immune checkpoints in the rat model of sepsis. Methods: We used 48 male Rattus norvegicus rats in this research and divided them into four groups: sham (rats without sepsis induction and treatment), control (sepsis-induced rats without treatment), T1 (sepsis-induced rats treated with 150 µL of secreted IL-10 from MSC), and T2 (sepsis-induced rats treated with 300 µL of secreted IL-10 from MSC). Forty-eight hours after sepsis induction, we terminated the rats and collected the blood to examine the PD-1 and PD-L1 expression levels. Results: We found a decrease in the relative expression of PD-1 in the septic rat group given 150 µL and 300 µL of secreted IL-10 from MSC compared to the control group, but the decrease was not significant. We also found a decrease in the relative expression of PD-L1 mRNA in the septic rat group given 150 µL and 300 µL of secreted IL-10 from MSC compared to the control group. Conclusion: Administering secreted IL-10 from MSC reduces the expression of PD-1 and PD-L1 in sepsis. These findings suggest that MSC secretome can improve the immunosuppression in sepsis.

The Role of Mesenchymal Stem Cell Secretome in the Inflammatory Mediators and the Survival Rate of Rat Model of Sepsis.

In sepsis, simultaneously elevated levels of pro-inflammatory cytokines and interleukin (IL)-10 indicate immune response dysregulation, increasing the mortality of the host. As mesenchymal stem cell (MSC) secretome is known to have immunomodulatory effects, we aim to assess the role of MSC secretome in the inflammatory mediators (NF-κB p65 and p50, TNF-α, IL-10) and the survival rate of a rat model of sepsis. In this study, forty-eight male Rattus norvegicus rats were divided into one sham group and three groups with sepsis induction: the control group and the sepsis-induced rat groups treated with 150 µL (T1) and 300 µL (T2) of secretome. The survival rate was observed per 6 h for 48 h and plotted using the Kaplan-Meier method. Compared to the control group, T2 showed a significant decrease in the relative expression of NF-κB and the serum TNF-α level, and a significant increase in the serum IL-10 level. Meanwhile, T1 showed a significant decrease in the serum TNF-α level compared to the control group. The Kaplan-Meier Log Rank test did not show significance in the distribution of survival between T1, T2, and the control group. However, from the 18th to the 36th hour, the survival rate of T2 was lower than the survival rate of the control group and T1, with a noticeable difference between T2 and the control group, as well as T1 at the 36th hour. At the 42nd hour, the survival rate of T2 was the same as the control group and remained lower than T1. In conclusion, MSC secretome regulated the inflammatory mediators in rat model of sepsis, with a dose of 150 µL being more effective.

The role of mesenchymal stem cells in allergic rhinitis and its relationship with IL-10, plasma cells and regulatory T cells.

Aim Allergic rhinitis (AR) is an IgE-mediated inflammation of the nose. Regulatory T cells (Tregs), plasma cells and inflammatory cytokines have shown to play a critical role in allergic airway inflammation. The aim of the study was to investigate the role of mesenchymal stem cells (MSCs) in generating Treg cells and plasma cells associated with regulating interlukin-10 (IL-10) in AR model. Methods Fifteen male Wistar rats (6 to 8 weeks old) were randomly divided into three groups (control group, sham group, and MSCs treatment group). Ovalbumin (OVA) nasal challenge was conducted daily from day 15 to 21, and MSCs (1x106) were administrated intraperitoneally to OVA-sensitized rats on day 21. Sneezing was observed from day 24 to 27. The rats were sacrificed on day 24 and day 27. The expression of Treg and plasma cells was analysed by flow cytometry assay. The level of IL-10 was analysed under ELISA assay. Results This study showed that the percentage of sneezing and rubbing times significantly decreased in MSCs treatment associated with the regulation of IL-10 level and plasma cell. This finding was aligned with the significant increase of Treg level. Conclusion MSCs administration regulates IL-10 and plasma cell-mediated immune and inflammatory responses while increasing Treg cell production. MSCs may be a promising therapeutic target for treating Treg-mediated allergic diseases.

Secretome of hypoxia-preconditioned mesenchymal stem cells enhance the expression of HIF-1a and bFGF in a rotator cuff tear model.

Aim To determine the effect of secretome hypoxia mesenchymal stem cells (SH-MSCs) on the relative gene expression of hypoxia inducible factor-1a (HIF-1a) and basic fibroblast growth factor (bFGF) in accelerating histomorphometric repair of tendon to bone interface healing in rats acute rotator cuff tear (RCT) model. Methods This is experimental research with posttest control group design. Thirty-male Wistar rats were divided into five treatment groups: healthy group and rotator cuff reconstruction group included four groups: SH-MSCs W2 (the treatment group was given a SH-MSCs 0.5 mL and terminated at weeks 2), NaCl W2 (the control vehicle group was given NaCl 0.5 mL and terminated at weeks 2), SH-MSCs W8 (the treatment group was given a SH-MSCs 0.5 mL and terminated at weeks 8), and NaCl W8 (the control vehicle group was given NaCl 0.5 mL and terminated at weeks 8). On the termination day, all the rats were terminated and HIF-1a and bFGF gene expression were analysed using qRT-PCR. Results SH-MSCs significantly increased the HIF-1a and bFGF gene expression than NaCl group even in week 2 and week 8. The highest increased gene expression of HIF-1a and bFGF was on week 8. Conclusion SH-MSCs are important in the healing repair process of tendon-to-bone interface in acute RCT model rats through increasing gene expression of HIF-1α and bFGF.

Red algae extract suppresses caspase-3 gene expression and induces catalase antioxidant enzyme in testicles of rats induced by boric acid.

Aim To determine the effect of red algae extract on the gene expression of catalase and caspase-3 in testicules of rats induced by boric acid (BA). Methods This is experimental research with post-test control group design. Twenty four healthy male Wistar rats were divided into four treatment groups: a healthy group, negative control group, two treatment groups with red algae extract 400mg/kgBW/day (T1) and red algae extract 800mg/kgBW/day (T2). Each group was treated with BA 500mg/kgBW/day for 14 days, whereas the healthy group did not receive BA. In the treatment groups T1 and T2 were given red algae extract for 14 days. On day 15 all treatment groups were terminated and catalase and caspase-3 gene expression were analysed using qRT-PCR. Results In the healthy group, the expression of the catalase gene was 1.39±0.67 and the expression of the caspase-3 gene was 1.06±0.17. In the negative control group, there was a significant decrease in catalase gene expression, 0.68±0.27 (p<0.05), and a significant increase in caspase-3 gene expression, 5.71±2.47 (p<0.05). Treatment groups T1 and T2 showed a significant increase in catalase gene expression, 2.67±0.69; and 2.85±0.64, respectively (p<0.05) and caspase-3, 3.96±1,16 and 1.89±0.84, respectively, compared to the control group. Conclusion: The administration of red algae extract had a significant effect on increasing the expression of the catalase gene and decreasing the expression of the caspase-3 gene. This suggests that red algae extract has the potential to be developed as a protective agent against exposure to the effects of BA.

Hypoxic secretome mesenchymal stem cells inhibiting interleukin-6 expression prevent oxidative stress in type 1 diabetes mellitus.

Aim Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the chronic inflammation of the pancreatic islets of Langerhans. Hyperglycaemia leads to suppressed antioxidant enzyme and increased inflammation in the pancreatic cell, resulting in pancreatic cell death. Hypoxic secretome mesenchymal stem cells (HS-MSCs) are soluble molecules secreted by MSCS that have the antiinflammation ability by secreting various cytokines including IL-10 and TGF-ß which potent as a promising therapeutic modality for T1DM. This study aims to investigate the role of HS-MSCs in regulating superoxide dismutase (SOD) and caspase-3 gene expression in T1DM model. Methods Twenty male Wistar rats (6 to 8 weeks old) were randomly divided into four groups (sham, control, HS-MSCs 0.5 mL and HS-MSCs 1 mL intraperitoneal treatment group). Streptozotocin (STZ) 60mg/kgBB was conducted once on day 1, HS-MSCs 0.5mL (T1) and HS-MSCs 1 mL (T2) were administrated intraperitoneally on day 7, 14, and 21 after STZ administration. The rats were sacrificed on day 28; the gene expression of SOD and IL-6 was analysed by qRT-PCR. Results This study showed that the ratio of SOD significantly increased in HS-MSCs treatment associated with suppression of IL-6 gene expression. Conclusion HS-MSCs administration suppresses oxidative stress and inflammation by up regulating SOD and inhibiting IL-6 to control T1DM.

Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Enhance Angiogenesis in Diabetic Rats with Peripheral Artery Disease.

Background: Lower limb peripheral artery disease (PAD) is the main risk of diabetes mellitus which result to high mortality rate. Approximately, 50% of patients who receive several treatments have passed away or lost limbs at a year's follow-up. Secretome of hypoxia mesenchymal stem cells (S-MSCs) contains several active soluble molecules from hypoxia MSCs (H-MSCs) that capable inducing anti-inflammatory and vascular regeneration in PAD. Objective: In this study, we investigated the therapeutic potential of S-MSCs in improving dynamic function and angiogenesis of PAD diabetic rats. Methods: The PAD was established by the incision from the groin to the inner thigh and distal ligation of femoral arteries in rats with diabetes. Rats were administered with 200 µL and 400 µL S-MSCs that successfully filtrated using tangential flow filtration (TFF) system based on various molecular weight cut-off categories intravenously. ELISA assay was used to analyze the cytokines and growth factors contained in S-MSCs. Tarlov score were examined at day 1, 3, 5, 7, 10 and 14. The rats were sacrificed at day 14 and muscle tissues were collected for immunohistochemistry (IHC) and gene expression analysis. Results: ELISA assay showed that S-MSCs provides abundant level of VEGF, PDGF, bFGF, IL-10 and TGFß. In vivo administration of S-MSCs remarkably enhanced the Tarlov score. S-MSCs improved angiogenesis through enhancing VEGF gene expression and significantly increasing CD31 positive area in muscle tissue of PAD diabetic rats. Conclusion: Our findings suggest that S-MSCs could improves dynamic function and angiogenesis in PAD diabetic rats.

Mesenchymal Stem Cells Suppress Dendritic Cells and Modulate Proinflammatory Milieu Through Interleukin-10 Expression in Peripheral Blood Mononuclear Cells of Human Systemic Lupus Erythematosus.

Background: Immune-mediated inflammatory injury among systemic lupus erythematosus (SLE) individuals may be involved by dendritic cells (DCs) abnormality though the underlying mechanism remains incompletely understood. Objective: This study aimed to elaborate MSCs' potential in suppressing abnormal DCs cell function on peripheral blood mononuclear cells (PBMCs) among SLE patients. Methods: MSCs were isolated from human umbilical cord blood. On the other side, human PBMCs were isolated from 20 active SLE patients and 5 healthy controls. The PBMCs of SLE patients were divided into 5 groups: sham (Sh) and control (C) groups were treated with standard medium, and the treatment groups (T1, T2 and T3) was co-cultured with hUC-MSC at doses of 1:1, 1:25, and 1:50 (MSCs:PBMCs). The expression of CD11c in DCs was analyzed using flow cytometry, while the level of TNF-α, IFN-γ, IL-6 and IL-10 was analyzed using cytometric bead array (CBA). Results: The MSCs significantly downregulates CD11c of dendritic cells in all treatment groups. MSCs also significantly suppress the level of TNF-α, IFN-γ, IL-6 and the significantly enhance IL-10 level in all treatment groups. Conclusion: Therefore, MSCs could suppress DCs through regulating the proinflammatory milieu in PBMCs of SLE patients.

Clitorea ternatea flower extract induces platelet-derived growth factor(PDGF) and GPx gene overexpression in ultraviolet (UV) B irradiationinduced collagen loss.

Aim To determine the effect of Clitorea ternatea flower extract (CTFE) in the gel dosage form on the expression of GPx and platelet-derived growth factor (PDGF) in ultraviolet (UV) - B irradiation-induced collagen loss rat model. Methods This is experimental research with post-test control group design. Twenty healthy male Wistar rats were divided into four treatment groups: a sham group, UVB control group, two treatment groups with gel of CTFE 5% and gel of CTFE 10%, respectively. Each group was treated with UVB at 302 nm with a MED of 160 mJ/cm2 for 5 days, whereas the sham group did not receive UVB. In the treatment groups CTFE 5% and CTFE 10% gel were given on the 6th to the 14th day. On day 14 all treatment groups were terminated, and GPx and PDGF gene expression were analysed using qRT-PCR. Results In the group of gel of CTFE 10%, there was a significant increase in GPx gene expression (9.51±1.83) and PDGF (4.36±1.18) compared to the UVB control group which had GPx and PDGF gene expression of 4.90±1.64) and 0.032±0.01, respectively. Conclusion The administration of CTFE gel showed an increase of the expression of GPx and PDGF g.

Water Extract Have Superior Cytotoxic Effect Than Ethanolic Extract of Clinacanthus Nutans Leaves in Breast Cancer Stem Cells.

Background: The rapid development of medical technology in managing breast cancer patients still cannot solve the problem of recurrence and resistance. One of the causes of recurrence and molecular resistance is the presence of breast cancer stem cells (BCSCs). Clinacanthus nutans (C.nutans) is a plant found in Medan, North Sumatra, Indonesia. This plant is believed to have anticancer activity in community. Objective: Our study aimed to assess phytochemical of C.nutans leaves, isolate breast cancer stem cells and determine the cytotoxic effects of the ethanolic extract and water extract of C.nutans leaves on breast cancer stem cells at 24, 48, and 72 h of observation. Methods: We underwent the cytotoxic test by using MTT assay and isolated breast cancer stem cells by using MACS and validated them by mammosphere test. Results: We found alkaloids, flavonoids, glycosides and tannins in simplicia and all extracts. BCSCs was valid with the diameter of the mammosphere BCSCs was > 60 µm. The IC50 values of 100%, 60%, 40%, 20% EE, and WE of C.nutans leaves were 227.30; 46.05; 31.12; 98.54, and 16.16 µg/ml respectively in the first 24 hours. In administering WE of C.nutans leaves, BCSCs viability was decreased at 24,48 and 72 hours of observation, namely 69.29±26%; 75.82 ± 21.02% and 38.94±9.34 % (p < 0.0001). Conclusion: The WE of C.nutans leaves had more substantial cytotoxic potential against BCSCs than the EE. The capability of WE C.nutans leaves to suppress BCSC's viability was time-dependent. The anticancer activity were believed originate from alkaloid and flavonoid group.

Locally injected Mesenchymal Stem Cells optimize angiogenesis by regulating VEGF and CD31 expression in duodenal perforation.

Background: Duodenal perforation is considered as one of gastrointestinal emergency with high morbidity and mortality rate. The MSCs have the ability to improve wound healing by releasing several growth factors and anti-inflammatory cytokines to promote the angiogenesis process. This study aimed to investigate the role of MSCs in duodenal perforation wound healing. Methods: MSCs were isolated from rat umbilical cord and injected into duodenal wound site at doses of 1.5x10 [(Putra et al., 2018) 66 cells for T1 group and 3x10 [(Putra et al., 2018) 66 cells for T2 group. The control group was treated by local injection of normal saline. The VEGF levels were measured by Western blot, while CD31 expression was analyzed using immunohistochemistry staining. All examinations were assessed on days 3 and 7. Results: Results showed a significant increase in VEGF and CD31 expression on days 3 and 7 (p < 0,05). The VEGF level was significantly decreased on day 7 compared to day 3. Conclusion: The administration of MSCs improved the angiogenesis process in duodenal perforation by enhancing VEGF and CD31 expression.

Topical gel of mesenchymal stem cells-conditioned medium under TNF-α precondition accelerates wound closure healing in full-thickness skin defect animal model.

Mesenchymal Stem Cells (MSCs) under TNF-α stimulation (MSC-CM-T) can release numerous trophic and survival molecules that have a promising prospect in wound healing acceleration. However, the effective levels of MSC-CM-T in topical gel preparation to accelerate wound healing should be further explored. The aim of this study was to investigate the effects of MSC-CM-T in topical gel preparation in accelerating optimal wound healing through analyzing PDGF levels, wound closure rate percentages, and fibroblast density appearances. Twenty-four male Wistar rats were performed a full-thickness excision. The group studies were randomly assigned into four subgroups: control gel, control medium, and two treatment groups: MSC-CM-T topical gel at doses of 100 µL and 200 µL (T1 and T2, respectively). Wound closure rates were measured by standard caliper, platelet-derived growth factor (PDGF) levels were analyzed using ELISA on days 3 and 6, whereas the fibroblast density appearances were determined using hematoxylin-eosin staining. This study found a significant increase in PDGF levels in all treatment groups on days 3 and 6. These findings were in line with the increase of wound closure rates in all treatment groups on day 6, in which the high dose of MSC-CM-T was more effective in initiating the increase of wound closure rate. We also found the fibroblast density appearances on day 6 in the T2 group. We conclude that the topical gel of MSC-CM-T is more effective in accelerating wound closure healing through increasing PDGF levels and wound closure percentages and fibroblast density appearances in the skin defect animal models.

Umbilical Cord-Derived Mesenchymal Stem Cells Improve TGF-ß, α-SMA and Collagen on Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats.

Background: A Erectile dysfunction (ED) is one of the well-known comorbidities in males with diabetes mellitus (DM), whose pathogenesis might be induced by dysregulation of corpus cavernosum smooth muscle cells. UC-MSCs are multipotent cells that attract considerable interest due to immunoregulatory properties and might be a potential strategy to regulate and recover the functional cells and tissues, including tissue improvement in DMED. Objective: This study aims to determine the efficacy of UC-MSCs in improving the erectile function of DMED rats through analyzing the expression of TGF-ß, α-SMA, and collagen. Methods: Total number of 30 male Sprague-Dawley rats (6 to 8 weeks old) were randomly divided into four groups (negative control group, positive control group, T1 group, and T2 group). After 16 h fast, 24 rats were randomly selected and intraperitoneally injected with streptozotocin to induce DM. At 8 weeks after STZ injection, rats with DMED were identified by unresponsive erectile stimulation within 30 min. PC group received 500 µL; T1 rats treated with 500 µL PBS containing 1x106 UC-MSCs; T2 rats treated with 500 µL PBS containing 3x106 UC-MSCs. After MSCs treatment, the rats were sacrificed and the corpus cavernosum tissues were prepared for histological observations. Results: This study resulted in the administration of UC-MSCs could downregulate the expression of TGF-ß, α-SMA, and collagen leading to the improvement of DMED. Conclusion: UC-MSCs improve the expression of TGF-ß, α-SMA, and collagen on erectile dysfunction in streptozotocin-induced diabetic rats.

Revealing the decrease of indoleamine 2,3-dioxygenase as a major constituent for B cells survival post-mesenchymal stem cells co-cultured with peripheral blood mononuclear cell (PBMC) of systemic lupus erythematosus (SLE) patients.

Aim Mesenchymal stem cells (MSCs) have potent immunosuppressive properties to control systemic lupus erythematosus (SLE) disease by inhibiting indoleamine 2,3-dioxygenase (IDO), and increasing regulatory T cells (Treg) to control innate and adaptive immune cells. However, the interaction and mechanism regarding IDO and B cells in the co-culture of MSC and SLE peripheral blood mononuclear cell (PBMCs) remain unclear. This study aimed to investigate the effects of MSCs in controlling B cells through IDO expression in PBMC of SLE patients. Methods This study used a post-test control group design. MSCs were obtained from human umbilical cord blood and characterized according to their surface antigen expression and multilineage differentiation capacities. PBMCs isolated from SLE patients were divided into five groups: sham, control, and three treatment groups. The treatment groups were treated by co-culturing MSCs to PBMCs with a ratio of 1:10, 1:25, and 1:40 for 72 h incubation. The B cell levels were analysed by flow cytometry with cytometric bead array (CBA) and the IDO levels were determined by ELISA. Results The percentages of B cells decreased significantly in groups treated by dose-dependent MSCs, particularly in T1 and T2 groups. These findings were aligned with the significant decrease of the IDO level. Conclusion MSCs control B cells-mediated by a decrease of IDO in PBMC of SLE patients.

Rats' umbilical-cord mesenchymal stem cells ameliorate mast cells and Hsp70 on ovalbumin-induced allergic rhinitis rats.

Aim Allergic rhinitis (AR) is a heterogeneous condition that has been associated with inflammatory responses and is characterized by clinical typical symptoms of nasal itching, sneezing, watery discharge and congestion. Mesenchymal stem cells (MSCs) are multipotent stem cells that have the immunoregulatory ability by secreting various cytokines which potent as a promising therapeutic modality for allergic airway diseases, including AR. The aim of this study was to investigate the effect of rat UC-MSCs on the number of mast cells, the expression of Hsp70 indicated by the nasal symptoms allergic, particularly nasal rubbing in ovalbumininduced AR rats. Methods Fifteen male Wistar rats (6 to 8 weeks old) were randomly divided into three groups (control group, sham group, and OVA+MSCs group). OVA nasal challenge was conducted daily from day 15 to 21, and UC-MSCs (1x106 ) were administrated intraperitoneally to OVA-sensitized rats on day 21. Nasal rubbing was observed from day 22 to 28. The rats were sacrificed on day 22 and day 28. The nasal cavity tissues were prepared for histological observations. Results The administration of UC-MSCs could reduce the number of mast cells and the expression of Hsp70 leading to reduction of nasal symptoms allergic, particularly nasal rubbing. Conclusion Based on this finding, MSCs present a promising immediate curative effect to the inflammatory reaction in AR rats.