Efficacy and Safety of Intravenous Mesenchymal Stem Cells for Ischemic Stroke

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011440
Author(s):  
Jong-Won Chung ◽  
Won Hyuk Chang ◽  
Oh Young Bang ◽  
Gyeong Joon Moon ◽  
Suk Jae Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Controlled Trial ◽  
Outcome Evaluation ◽  
Autologous Serum ◽  
Secondary Outcome ◽  
Control Group ◽  
Link Type ◽  
Significant Difference ◽  
Major Stroke

ObjectiveTo test whether autologous modified mesenchymal stem cells (MSCs) improve recovery in patients with chronic major stroke.MethodsIn this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct within 90 days of symptom onset were assigned, in a 2:1 ratio, to receive preconditioned autologous MSC injections (MSC group) or standard treatment alone (control group). The primary outcome was the score on the modified Rankin Scale (mRS) at 3 months. The secondary outcome was to further demonstrate motor recovery.ResultsA total of 39 and 15 patients were included in the MSC and control groups, respectively, for the final intention-to-treat analysis. Mean age of patients was 68 (range, 28–83) years, and mean interval between stroke onset to randomization was 20.2 (range, 5–89) days. Baseline characteristics were not different between groups. There was no significant difference between the groups in the mRS score shift at 3 months (p = 0.732). However, secondary analyses showed significant improvements in lower extremity motor function in the MSC group compared to the control group (change in the leg score of the Motricity Index, p = 0.023), which was notable among patients with low predicted recovery potential. There were no serious, treatment-related adverse events.ConclusionsIntravenous application of preconditioned, autologous MSCs with autologous serum was feasible and safe in patients with chronic major stroke. MSC treatment was not associated with improvements in the 3-month mRS score, but we did observe leg motor improvement in detailed functional analyses.Classification of evidenceThis study provides Class III evidence that autologous mesenchymal stem cells do not improve 90-day outcomes in patients with chronic stroke.Trial registrationclinicaltrials.gov Identifier: NCT01716481.

scholarly journals Clinical Efficacy of Arthroscopic Therapy With Infrapatellar Fat Pad Cell Concentrates in Treating Knee Cartilage Lesion: a Randomized Controlled Trial

2020 ◽  
Author(s):  
Yiqin Zhou ◽  
Haobo Li ◽  
Dong Xiang ◽  
Jiahua Shao ◽  
Qiwei Fu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Clinical Efficacy ◽  
Controlled Trial ◽  
Cartilage Lesion ◽  
Infrapatellar Fat Pad ◽  
Control Group ◽  
Knee Cartilage ◽  
Fat Pad ◽  
Significant Difference

Abstract Background: Toevaluatethe clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesion, we launched a prospective randomized single-blind clinical study of controlled method.Methods: 60 cases from Shanghai Changzheng Hospital during April 2018 to December 2019 were chosen and randomlydivided into 2 groups equally. Patients in the experiment group were treated throughknee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stem cells, while patients in the control group were treated through regular knee arthroscopic therapy. VAS and WOMAC scores were assessed at pre-operation, and 6 weeks, 12 weeks, 6 months, 12 months after intervention. MORCART scores were assessed at pre-operation and 12 months after intervention.Results: 29 cases in the experiment group and 28 cases in the control group were followed up. No significant difference in VAS, WOMAC, and MOCART scores were found between the two groups before surgery(P>0.05). The WOMAC-Total and WOMAC-Function scores ofexperiment groupwere significantly lower than those of control group 6 months, 12 months after surgery(P<0.05). The VAS-Rest and VAS-Motion scoresofexperiment group were found significantly lower than those of control group 12 months after surgery(P<0.05).The MOCART scores of experiment group were found significant higher compared with control group12 months after surgery(P<0.05). No significant difference in WOMAC-Stiffness scores were found between the two groups.Conclusions:The short-term results of our study are encouraging and demonstrate that knee arthroscopy with infrapatellar fat pad cell concentrates containing mesenchymal stem cells is safe, and provides assistance in reducing pain and improvingfunction in patients with knee cartilage lesion.Trial registration: ChiCTR1800015379. Registered on 27 March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25901.

scholarly journals Clinical efficacy on glycemic control and safety of mesenchymal stem cells in patients with diabetes mellitus: Systematic review and meta-analysis of RCT data

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247662
Author(s):  
Jingjing He ◽  
Desheng Kong ◽  
Zhifen Yang ◽  
Ruiyun Guo ◽  
Asiamah Ernest Amponsah ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Random Effects ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
Significant Difference

Background Diabetes mellitus as a chronic metabolic disease is threatening human health seriously. Although numerous clinical trials have been registered for the treatment of diabetes with stem cells, no articles have been published to summarize the efficacy and safety of mesenchymal stem cells (MSCs) in randomized controlled trials (RCTs). Methods and findings The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to provide a reliable numerical summary and the most comprehensive assessment of therapeutic efficacy and safety with MSCs in diabetes. PubMed, Web of Science, Ovid, the Cochrane Library and CNKI were searched. The retrieval time was from establishment of these databases to January 4, 2020. Seven RCTs were eligible for analysis, including 413 participants. Meta-analysis results showed that there were no significant differences in the reduction of fasting plasma glucose (FPG) compared to the baseline [mean difference (MD) = -1.05, 95% confidence interval (CI) (-2.26,0.16), P<0.01, I2 = 94%] and the control group [MD = -0.62, 95%CI (-1.46,0.23), P<0.01, I2 = 87%]. The MSCs treatment group showed a significant decrease in hemoglobin (Hb) A1c [random-effects, MD = -1.32, 95%CI (-2.06, -0.57), P<0.01, I2 = 90%] after treatment. Additionally, HbA1c reduced more significantly in MSC treatment group than in control group [random-effects, MD = -0.87, 95%CI (-1.53, -0.22), P<0.01, I2 = 82%] at the end of follow-up. However, as for fasting C-peptide levels, the estimated pooled MD showed that there was no significant increase [MD = -0.07, 95%CI (-0.30, 0.16), P<0.01, I2 = 94%] in MSCs treatment group compared with that in control group. Notably, there was no significant difference in the incidence of adverse events between MSCs treatment group and control group [relative risk (RR) = 0.98, 95%CI (0.72, 1.32), P = 0.02, I2 = 70%]. The most commonly observed adverse reaction in the MSC treatment group was hypoglycemia (29.95%). Conclusions This meta-analysis revealed MSCs therapy may be an effective and safe intervention in subjects with diabetes. However, due to the limited studies, a number of high-quality as well as large-scale RCTs should be performed to confirm these conclusions.

scholarly journals Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model

2021 ◽  
Vol 40 (1) ◽  
pp. 29
Author(s):  
Nur Anna C Sa’dyah ◽  
Agung Putra ◽  
Bayu Tirta Dirja ◽  
Nurul Hidayah ◽  
Salma Yasmine Azzahara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Significant Difference ◽  
T1 And T2

Introduction<br />Liver fibrosis (LF) results from the unregulated chronic wound healing process in liver tissue. Transforming growth factor-beta (TGF-β) is the major contributing cytokine of LF promotion through activation of quiescent hepatic stellate cells (HSCs) into myofibroblasts (MFs) and increased extracellular matrix (ECM) deposition such as collagen leading to scar tissue development. Mesenchymal stem cells (MSCs) have an immunomodulatory capability that could be used as a new treatment for repairing and regenerating LF through suppression of TGF-β. This study aimed to examine the role of MSCs in liver fibrosis animal models through suppression of TGF-β levels without scar formation particularly in the proliferation phase.<br /><br />Methods<br />In this study, a completely randomized design was used with sample size of 24. Male Sprague Dawley rats were injected intraperitoneally (IP) with carbon tetrachloride (CCl4), twice weekly, for eight weeks to induce LF. Rats were randomly assigned to four groups: negative control, CCl4 group, and CCL4 + MSC-treated groups T1 and T2, at doses of 1 x 106 and 2x106 cells, respectively. TGF-β levels were analyzed by enzyme-linked immunosorbent assay (ELISA). One-way ANOVA and a least significant difference (LSD) was used to analyse the data. <br /><br />Results<br />The TGF levels of LF rat models decreased on day 7 after MSC administration. The levels of TGF-β in both MSC groups T1 and T2 decreased significantly compared with the control group (p&lt;0.05). The TGF-β suppression capability of T2 was optimal and more significant than that of T1.<br /><br />Conclusion<br />MSCs can suppress TGF levels in liver fibrosis induced rats.

scholarly journals Gothenburg Very Early Supported Discharge study (GOTVED): a randomised controlled trial investigating anxiety and overall disability in the first year after stroke

BMC Neurology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lena Rafsten ◽  
Anna Danielsson ◽  
Asa Nordin ◽  
Ann Björkdahl ◽  
Asa Lundgren-Nilsson ◽  
...  
Keyword(s):  
Multidisciplinary Team ◽  
Controlled Trial ◽  
Stroke Care ◽  
Secondary Outcome ◽  
Outpatient Rehabilitation ◽  
Control Group ◽  
Stroke Patients ◽  
Post Stroke ◽  
Early Supported Discharge ◽  
Significant Difference

Abstract Background and purpose Early supported discharge (ESD) has been shown to be efficient and safe as part of the stroke care pathway. The best results have been seen with a multidisciplinary team and after mild to moderate stroke. However, how very early supported discharge (VESD) works has not been studied. The aim of this study was to investigate whether VESD for stroke patients in need of ongoing individualized rehabilitation affects the level of anxiety and overall disability for the patient compared with ordinary discharge routine. Methods A randomized controlled trial was performed with intention to treat analyses comparing VESD and ordinary discharge from hospital. All patients admitted at the stroke care unit at Sahlgrenska University Hospital of Gothenburg between August 2011 and April 2016 were screened. Inclusion occurred on day 4 using a block randomization of 20 and with a blinded assessor. Assessments were made 5 days post-stroke and 3 and 12 months post-stroke. Patients in the VESD group underwent continued rehabilitation in their homes with a multidisciplinary team from the stroke care unit for a maximum of 1 month. The patients in the control group had support as usual after discharge when needed such as home care service and outpatient rehabilitation. The primary outcome was anxiety as assessed by the Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A). The secondary outcome was the patients’ degree of overall disability, measured by the modified Rankin Scale (mRS). Results No significant differences were found between the groups regarding anxiety at three or 12 months post-stroke (p = 0.811). The overall disability was significantly lower in the VESD group 3 months post-stroke (p = 0.004), compared to the control group. However, there was no significant difference between the groups 1 year post-stroke. Conclusions The VESD does not affects the level of anxiety compared to ordinary rehabilitation. The VESD leads to a faster improvement of overall disability compared to ordinary rehabilitation. We suggest considering coordinated VESD for patients with mild to moderate stroke in addition to ordinary rehabilitation as part of the service from a stroke unit. Trial registration Clinical Trials.gov: NCT01622205. Registered 19 June 2012 (retrospectively registered).

The Reverse Remodeling Effect of Mesenchymal Stem Cells is Independent from the Site of Epimyocardial Cell Transplantation

2013 ◽  
Vol 8 (6) ◽  
pp. 433-439 ◽  
Author(s):  
Mani Arsalan ◽  
Stefan Dhein ◽  
Heike Aupperle ◽  
Ardawan Julian Rastan ◽  
Markus Jan Barten ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sham Group ◽  
Heart Function ◽  
Capillary Density ◽  
Left Ventricular ◽  
Reverse Remodeling ◽  
Control Group ◽  
Positive Effects ◽  
Significant Difference

Objective The transplantation of mesenchymal stem cells (MSCs) represents a promising approach for treating the ischemic and the nonischemic diseased heart. The positive effects of transplanting these cells could be shown, but the exact mechanisms remain unknown. We evaluated whether the injection site affects the improvement in left ventricular (LV) ejection fraction (EF) and angiogenesis in doxorubicin (Dox)–induced failing hearts. Methods Heart failure was induced in New Zealand white rabbits by doxorubicin treatment, followed by right ventricular MSC transplantation (RV-MSC, n = 6), LV MSC transplantation (LV-MSC, n = 6), sham treatment (sham group, n = 6), or no therapy (Dox group, n = 5). Healthy rabbits were used as control group (n = 8). Cells were isolated after bone marrow aspiration and transplanted locally into the ventricular myocardium. After 4 weeks, cardiac function and capillary density (CD31 staining) were measured. Results The transplantation of MSCs increased the EF significantly (LV-MSC, 39.0% ± 1.4%, and RV-MSC, 39.2% ± 2.6%, vs sham group, 29.8% ± 3.7%; P < 0.001), without significance between the MSC groups ( P = 0.858). Neither the evidence of a transdifferentiation nor any signs of cell engraftment of transplanted cells could be found. The capillary density (capillaries/high-power field) increased in both MSC groups compared with the sham group (LV-MSC by 8.3% ± 3.4%; and RV-MSC, 8.1% ± 2.2%; P < 0.05), without significance between the two MSC groups ( P = 0.927). Conclusions Injection of autologous MSCs in doxorubicin-induced cardiomyopathic rabbit hearts improves EF and enhances angiogenesis. Despite local application, we observed global effects on heart function and capillary density without significant difference between right and LV injection. The paracrine mechanism might be one possible explanation for these findings.

scholarly journals Randomized Controlled Trial of Probiotic PS128 in Children with Tourette Syndrome

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3698
Author(s):  
Chang-Chun Wu ◽  
Lee-Chin Wong ◽  
Chia-Jui Hsu ◽  
Chianne-Wen Yang ◽  
Ying-Chieh Tsai ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Tourette Syndrome ◽  
Performance Test ◽  
Controlled Trial ◽  
Continuous Performance Test ◽  
Secondary Outcome ◽  
Control Group ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Social Environmental

Tourette syndrome results from a complex interaction between social–environmental factors, multiple genetic abnormalities, and neurotransmitter disturbances. This study is a double-blinded, randomized controlled trial using probiotics Lactobacillus plantarum PS128 as an intervention to examine if probiotics improve symptoms of children with Tourette syndrome. This study enrolled children aged 5 to 18 years old who fulfilled DSM-V diagnostic criteria for Tourette syndrome. Patients were assessed before initiating the trial, at one month, and at two months after randomization. The primary outcome was evaluated by Yale Global Tic Severity Scale (YGTSS), and the secondary outcome studied the possible comorbidities in these children. The results revealed no significant difference in improvement in YGTSS between the control group and the PS128 group. As for secondary endpoints, an analysis of Conners’ Continuous Performance Test (CPT) showed improvement in commission and detectability in the PS128 group. In conclusion, although probiotics may not have tic-reducing effects in children with Tourette syndrome, it may have benefits on comorbidities such as attention deficit and hyperactivity disorder (ADHD). Further studies are needed to clarify the effects of probiotics on the comorbidities of Tourette syndrome children.

scholarly journals Functional and Radiological Comparison of Umbilical Cord Mesenchymal Stem Cells, Somatotropin, and Hyaluronic Acid Injection for Cartilage Repair in Early Osteoarthritis of the Knee: A Randomized Controlled Trial

2020 ◽  
Vol 8 (5_suppl5) ◽  
pp. 2325967120S0004
Author(s):  
J Fiolin ◽  
IH Dilogo ◽  
AMT Lubis ◽  
JA Pawitan ◽  
IK Liem ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hyaluronic Acid ◽  
Knee Osteoarthritis ◽  
Umbilical Cord ◽  
Controlled Trial ◽  
Osteoarthritis Of The Knee ◽  
Significant Difference ◽  
Group A ◽  
Ikdc Score

The umbilical cord-mesenchymal stem cells (UC-MSC) has been shown to improve the viability of degenerated chondrocytes in knee osteoarthritis (KOA) in cellular level. Additional somatotropin injection also shown clinical improvement in patients. The present trial is conducted to assess the efficacy of umbilical cord mesenchymal stem cells (UC-MSC) in comparison to somatotropin and hyaluronic acid (HA) injection to treat and slow the progression of knee osteoarthritis. Methods: This study was conducted from January 2016 to April 2018 in Cipto Mangunkusumo General Hospital. A total of 28 knees from 15 patients with early KOA Kellgren Lawrence I-II were randomized into three groups. Group A was treated with 1x106 units of intra-articular UC-MSCs + 2 ml HA followed with 2 consecutive weeks of HA injection; group B was treated with the same dose of HA with additional 8 IU of Somatotropin; group C was treated as control. The International Knee Documentation Committee (IKDC) score, The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analogue score (VAS), were assessed on the 1st and 3rd month, then every 3rd month until 12 months. Cartilage evaluation using MRI cartigram were performed at pre-implantation, and after the 6th and 12th month after implantation Results: General improvement were observed in all groups after 6 and 12 months. The IKDC score improved significantly among groups after 12 months (69.43 [48.3-89.66], 79.31 [51.72-90.08], and 75.9 [67.82-97.7] in group A, B, and C, respectively, p =0.005). We did not find a significant difference between groups in VAS and WOMAC results. However, we observed a medial T2 improvement in group A (39.55 [32.65-67.85] initially and 45.64 [38.12-70.65] 12 months after implantation). Conclusion: Injection of UC-MSC could improve knee function and cartilage profile in early KOA. However, further multicenter studies with larger samples are required to investigate the efficacy of such treatment for treating knee osteoarthritis.

scholarly journals Does Nursery-Based Intensified Anticipatory Guidance Reduce Emergency Department Use for Nonurgent Conditions in the First Month of Life? A Randomized Controlled Trial

2016 ◽  
Vol 2016 ◽  
pp. 1-6
Author(s):  
Kelly Kamimura-Nishimura ◽  
Vikram Chaudhary ◽  
Folake Olaosebikan ◽  
Maryam Azizi ◽  
Sneha Galiveeti ◽  
...  
Keyword(s):  
Emergency Department ◽  
Controlled Trial ◽  
Intervention Group ◽  
Newborn Care ◽  
Secondary Outcome ◽  
Control Group ◽  
Anticipatory Guidance ◽  
Guidance Program ◽  
Significant Difference ◽  
The Impact

Objective.We aimed to evaluate the impact of an intensified anticipatory guidance program in the nursery on Emergency Department (ED) use for nonurgent conditions (NUCs) in the neonatal period.Methods. Parturient mothers of healthy newborns were randomized to an intervention group or control group. Baseline and 1-month follow-up knowledge surveys regarding newborn care were conducted. The primary outcome was the proportion of neonates who used the ED for a NUC. Secondary outcome was change in caregivers’ knowledge on NUC.Results. Of a total of 594 mothers, 323 (54%) agreed to participate and were randomized to intervention (n=170) or control (n=153) group. Most were Hispanic (68%), single (61%), primiparous (39%), and without high school diploma (44%). 35 (21%) neonates in the intervention group and 41 (27%) in the control group were brought at least once for a NUC to the ED (p=0.12). There was no statistically significant difference in within subject change on knowledge scores between the two study arms.Conclusions. Neonatal ED visits for NUCs occur frequently. This nursery-based intensified anticipatory guidance program had no statistically significant impact on neonatal ED use for NUC, nor on neonatal care-relevant knowledge among parturient mothers. Alternative modalities and timing of parental educational intervention may need to be considered. This trial is registered with Clinical Trials NumberNCT01859065(Clinicaltrials.gov).

scholarly journals The Effect of Adipose Tissue-Derived Mesenchymal Stem Cells on Regeneration of Uterine Scars

2017 ◽  
Vol 23 (3) ◽  
pp. 120
Author(s):  
R. Ada Bender ◽  
Aykan Yücel ◽  
Volkan Noyan ◽  
Aylin Gürpınar ◽  
Pınar Atasoy ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Control Group ◽  
Optimum Level ◽  
Wound Recovery ◽  
Significant Difference ◽  
Histopathological Effects ◽  
Mesenchyme Stem Cells

<p><strong>OBJECTIVE:</strong> The mesenchymal stem cell application to uterine healing scars may provide better tissue strength.<br /><strong>STUDY DESIGN:</strong> Hysterectomy was performed on rats, and the wound recovery as a result of primary suturing was evaluated as tissue stretching and the positive histopathological effects. The mesenchymal stem cells originating from the adipose tissue were used during the healing period of the wound and would differentiate to mesenchyme-originated cells present in intact tissue for an optimum level of healing.<br /><strong>RESULTS:</strong> The weights of non-incised uterine horns in the control group were found to be significantly higher than the weights of the incised uterine horns (z=2.52, p=0.012). In the experiment group, the weights of the incised uterine horns were found to be significantly higher than the non-incised uterine horns (z=2.527, p=0.012). In the control group, the non-incised uterine horns withstood the stretching test to a higher extent than the incised horns, and a significant difference was found between the stretching values (z=2.51, p=0.012). In the experiment group, the incised uterine horns withstood the stretching tests to a higher extent than the non-incised uterine horns; however, there was no significant difference between the stretching tests (z=1.540, p=0.123).<br /><strong>CONCLUSION:</strong> Adipose tissue-originated mesenchyme stem cells were observed to increase the tissue stretching during wound healing.<br /><br /></p>

scholarly journals Immunolocalization of Steroidogenic Enzymes (3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, and P450scc) in Rats with Testicular Dysfunction Treated with Mesenchymal Stem Cells-conditioned Medium

2021 ◽  
Vol 11 (3) ◽  
pp. 368-376
Author(s):  
Linda Miftakhul Khasanah ◽  
Teguh Budipitojo ◽  
Yuda Heru Fibrianto
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Leydig Cells ◽  
Hydroxysteroid Dehydrogenase ◽  
Treated Group ◽  
Control Group ◽  
Testicular Dysfunction ◽  
Significant Difference ◽  
Injection Dose

About 60-80 million couples in the world are suffering from infertility disease. Infertility is a major problem in patients coping with chemotherapy. The chemotherapy process can degenerate non-target organs, especially in testes. Infertility in male or testicular dysfunction is caused by the failure of proliferation and differentiation of the spermatogenic cells. Many studies reported that mesenchymal stem cells-conditioned medium promoted regenerative processes. The present study aimed to investigate the effect of mesenchymal stem cells-conditioned medium on the cisplatin-induced testicular dysfunction by examining the immunolocalization of steroidogenic enzymes, such as 3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, and P450scc which are considered as markers of steroid production. All experimental animals were divided into three groups, namely the control group, mesenchymal stem cells-conditioned medium treated group with an injection dose of 0.2 ml/kg body weight (BW, P1), and mesenchymal stem cells-conditioned medium treated group with an injection dose of 0.5 ml/kg BW (P2). Cisplatin was injected into both treated groups to induce testicular dysfunction. The testicular tissues were processed by the paraffin method, then cut to a thickness of 5 µm, followed by immunohistochemical staining. The HSD3B1 immunoreactivities were found only in Leydig cells, and the intensity increased every week after the injection of mesenchymal stem cells-conditioned medium. The variety of weeks and groups was significantly different in the number of immunoreactive cells of HSD3B1. The results indicated a significant difference between one week after the first injection and the one week after the third and fourth injection. The findings showed a significant difference between the treated group with an injection dose of 0.2 ml/kg BW and the control group. The number of immunoreactive cells of HSD3B1 with an injection dose of 0.5 ml/kg BW was greater compared to the group that received an injection dose of 0.2 ml/kg BW. The intensity of HSD3B1 and HSD17B1 increased every week. The p450scc immunoreactive cells were only found in Leydig cells. The intensity of positive cells of p450scc in the treated group with an injection dose of 0.5 ml/kg BW was more intense, compared to the treated group with an injection dose of 0.2 ml/kg BW. The results of the current study showed that the injection of mesenchymal stem cells-conditioned medium can improve the regeneration of spermatogenic cells, and recover spermatogenesis proved by positive cells of HSD3B1, HSD17B1, and p450scc as markers of steroid production.

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