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.

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Assessment of the Role of NOGO Gene Block in Enhancing the Neuro-regenerative Effect of Mesenchymal Stem Cells.

10.21203/rs.3.rs-137171/v1 ◽

2021 ◽

Author(s):

Eman Youssef ◽

Hala Gabr ◽

Nirmeen A Kishk ◽

Maha Baligh Zickri ◽

Shahira KA Botros ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Treatment Group ◽

Glial Cells ◽

Therapeutic Potential ◽

P Value ◽

P Values ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract Background: Amyotrophic Lateral Sclerosis (ALS) is a fatal disease. Mesenchymal stem cells (MSCs) have a therapeutic potential in neuronal diseases, factors as NOGO-A limit axonal regeneration. In this study, gene silencing was used to suppress Nogo-A expression in MSCs to enhance its neuro-regenerative role. Methods: mouse models of motor neuron degeneration were created, effect of non-modified and plasmid transfected MSCs were studied clinically and histologically. Group 1 received no treatment. Group 2 received IV injection of non modified MSCs and sacrificed after 8 days (subgroup 2a) and 15 days (subgroup 2b) following treatment, Group 3 received IV injection of transfected MSCs and were sacrificed after 8 days (subgroup 3a) and 15 days (subgroup 3b) following treatment. Results: A significant increase in weight and motor scores of subgroups 2a & 2b occurred in comparison to subgroups1a & 1b respectively (p values <0.001, <0.001, 0.001 & 0.026 respectively), GAP43 expression in group 2 mice was significantly higher compared to group 1 mice (p value <0.001). Deformed neurons and glial cells in group 2 were significantly lower compared to group 1 mice (p value <0.001). Deformed neurons and glial cells in subgroup 2b were significantly less in comparison to subgroup 2a (p values = 0.002 and 0.03) indicating an improvement with time. GAP43 in subgroup 2b was significantly higher compared to subgroup 2a (p value = 0.030).Weight and motor power in group 3 mice was significantly higher when compared to group 1 on days; 14 and 21 (p values <0.001, <0.001, <0.001 and 0.008) respectively. Deformed neurons and glial cells in group 3 mice were significantly lower when compared to group 1 mice (p values <0.001). GAP43 expression in group 3 mice was significantly higher when compared to group1 (p value <0.001). Deformed neurons in subgroup 3b was significantly less than subgroup 3a (p value <0.001). GAP43 expression in group 3 mice was significantly increased when compared to group 2 mice (p value <0.001).Conclusion: NOGO-A gene SiRNA is a potential enhancer of the neuro-regenerative action of MSCs.

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Differentiation of bone marrow derived mesenchymal stem cells into male germ-like cells in co-culture with testicular cells

Endocrine Regulations ◽

10.2478/enr-2019-0011 ◽

2019 ◽

Vol 53 (2) ◽

pp. 93-99

Author(s):

Nasim Malekmohamadi ◽

Alireza Abdanipour ◽

Mehrdad Ghorbanlou ◽

Saeed Shokri ◽

Reza Shirazi ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Treatment Group ◽

Mouse Bone Marrow ◽

Testicular Cells ◽

Morphogenetic Protein ◽

Group 2 ◽

Group 1

AbstractObjective. Stem cell therapy, specifically, pre-induction of mesenchymal stem cells toward male germ-like cells may be useful in patients with azoospermia. The aim of this study was to evaluate in vitro differentiation of mouse bone marrow-derived mesenchymal stem cells (BMSCs) into male germ-like cells by indirect co-culture with testicular cells in the presence of bone morphogenetic protein 4 (BMP4).Methods. Experimental groups included: control (mouse BMSCs), treatment group-1 (BMSCs treated with BMP4), treatment group-2 (indirect co-culture of BMSCs with mouse testicular cells in the presence of BMP4) and treatment group-3 (indirect co-culture of BMSCs with testicular cells). BMSCs-derived male germ-like cells were evaluated by the expression of Dazl, and Stra8 using RT-qPCR.Results. Stra8 gene expression was significantly increased in the treatment group-2 and Dazl gene was significantly increased in the treatment group-1 compared to other groups. In conclusion, indirect co-culturing of BMSCs with testicular cells and BMP4 leads to the differentiation of BMSCs into male germ-like cells which express specific male germ-like genes. Testicular cells released factors that contributed to the differentiation of BMSCs into male germ progenitor cells.Conclusion. This study suggests that mesenchymal stem cells may be differentiated into male germ-like cells and therefore, may be a novel treatment option for men with azoospermia.

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The Clinical Research of Umbilical Cord Blood Transplantation for Children with Leukemia or Whom with Beta-Thalassemia.

Blood ◽

10.1182/blood.v106.11.5435.5435 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5435-5435

Author(s):

Jianpei Fang ◽

Shaoling Huang ◽

Dunhua Zhou

Keyword(s):

Cord Blood ◽

Umbilical Cord Blood ◽

Acute Gvhd ◽

Cord Blood Transplantation ◽

Umbilical Cord Blood Transplantation ◽

Post Transplantation ◽

Blood Transplantation ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract Objective To evaluate the clinical efficacy and complications of related (RD) umbilical cord blood transplantation (UCBT) or unrelated (UD) UCBT for children with leukemia or whom with b-thalassemia (TM). Methods Ten patients with TM received RD-UCBT (group 1), while another 10 patients with TM had UD-UCBT (group 2).13 patients with leukemia (4 high risk ALL and 9 AML) were transplanted from UD-UCB (group3). Of 7 were HLA-identical, a patient was a loci-mismatched and two of them were half matched in group 1. Meanwhile, in the group2, three of ten patients were HLA matched, six was a loci-mismatched and one received double unites of UD-UCB that was from HLA matched to a loci-mismatched. Furthermore, ten of 13 patients were one loci-mismatched in group 3. Two were two loci-mismatched and one received double unites of UD-UCB from HLA matched to a loci-mismatched in the group. The conditioning regimen was consisted of busulfan (Bu) 14–20 mg /kg, cyclophosphages(Cy) 120–200 mg /kg and horse antithymocyte globulin (ATG)90 mg /kg or rabbit ATG 25 mg /kg for all TM patients. Of them, 6 also received melphalan (Melph) 90 mg /m2. Four patients had fludarabine (Flu) 150 mg /m2. Three combined Flu with thiotepa (TT) 6 mg /kg. Five used Flu, TT and TBI together. In the group of patients with leukemia (group 3), the regimen was divided into two branches: (1) Non-TBI regimen: the regimen mainly focused on 10 patients with leukemia in the CR phase except a patient was too young although him in the NR phase, which was consisted of Bu, Cy, ATG and Flu. A patient added high dose Ara-C. One had IDA, and 3 Melph. (2). Accompanying with TBI regimen. Only had two patients who were in the phase of NR used this regimen. The dose of TBI was 7.5 Gy and 6.5 Gy respectively. The patients received the nucleated cells 7.5 (3.4–19.4)’107/kg, CD34 cell 4.5 (0.6–11.7) ’105/kg, CFU-GM 1.1 (0.2–23) ’105/kg in three groups. Result: The engraftment occurred 7 in 10 at the group 1. One patient developed acute GVHD grade III. Two patients rejected 2 months post RD-UCBT. The following up was from 34–69 months in the group and 4 cases remained in the EFS. However, only 3 out of 10 were engraftment in the group 2. The others all were antologous reconstitution in the failure patients. One developed acute GVHD grade II in the group 2. The following up was from 3 months to 43 months in the group. Two cases kept EFS but one died of IP at the 6 months post transplantation. 11 out of 13 patients engrafted in the group 3. Nine patients were EFS post transplantation and the time of following up was from 4 to 37 months in the group. One developed severe acute GVHD and 3 had extensive chronic GVHD.

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Management of toxic optic neuropathy via a combination of Wharton’s jelly-derived mesenchymal stem cells with electromagnetic stimulation

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02577-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Emin Özmert ◽

Umut Arslan

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Optic Neuropathy ◽

Electromagnetic Stimulation ◽

Toxic Optic Neuropathy ◽

Delta Change ◽

Group 3 ◽

The Mean ◽

Group 2 ◽

Group 1

Abstract Purpose To investigate the effect of the combination of Wharton's jelly derived mesenchymal stem cells (WJ-MSC) and high frequency repetitive electromagnetic stimulation (rEMS) in the therapy of toxic optic neuropathies with severe symptoms after the available current therapy modalities which were unsucessful. Material and methods This prospective, open-label clinical phase-3 study was conducted at Ankara University Faculty of Medicine, Department of Ophthalmology between April 2019 and April 2021. Thirty-six eyes of 18 patients with toxic optic neuropathy (TON) were included in the study. Within 1–3 months after the emergency interventions, patients with various degrees of sequela visual disturbances were studied in this clinical trial. The cases were divided into three groups according to similar demographic characteristics. Group 1: Consists of 12 eyes of 12 patients treated with the WJ-MSC and rEMS combination in one eye. Group 2: Consists of 12 eyes of 12 patients treated with only rEMS in one eye. Group 3: Consists of 12 eyes of six patients treated with only WJ-MSC in both eyes. The course was evaluated by comparing the quantitive functional and structural assessment parameters measured before and at the fourth month of applications in each group. Results The mean best corrected visual acuity (BCVA) delta change percentages of the groups can be ranked as: Group 1 (47%) > Group 3 (32%) > Group 2 (21%). The mean fundus perimetry deviation index (FPDI) delta change percentages of the groups can be ranked as: Group 1 (95%) > Group 2 (33%) > Group 3 (27%). The mean ganglion cell complex (GCC) thickness delta change (decrease in thickness) percentages can be ranked as: Group 1 (− 21%) > Group 3 (− 15%) > Group 2 (− 13%). The visual evoked potential (VEP) P100 latency delta change percentages of the groups can be ranked as: Group 1 (− 18%) > Group 3 (− 10%) > Group 2 (− 8%). The P100 amplitude delta change percentages of the groups can be ranked as: Group 1 (105%) > Group 3 (83%) > Group 2 (24%). Conclusion Toxic optic neuropathies are emergent pathologies that can result in acute and permanent blindness. After poisoning with toxic substances, progressive apoptosis continues in optic nerve axons and ganglion cells. After the proper first systemic intervention in intensive care clinic, the WJ-MSC and rEMS combination seems very effective in the short-term period in cases with TON. To prevent permanent blindness, a combination of WJ-MSC and rEMS application as soon as possible may increase the chance of success in currently untreatable cases. Trial Registration ClinicalTrials.gov ID: NCT04877067.

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Adipose-derived Mesenchymal Stem Cells Improve the Healing of Tracheoesophageal Fistula in a Beagle Model

10.21203/rs.3.rs-146858/v1 ◽

2021 ◽

Author(s):

Yuchao Wang ◽

Shifang Yang ◽

Pingping Chen ◽

Hanyi Xu ◽

Jinghua Cui ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Tracheoesophageal Fistula ◽

Saline Water ◽

Clinical Problem ◽

Endoscopic Observation ◽

Volume Group ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract Background Tracheoesophageal fistula (TEF) is still a devastating clinical problem with high mortality. New clinical strategies were developed to sustain survival time. Mesenchymal stem cells were applied in many clinical wound healing fields. This study aims to investigate the main effect of stem cell to TEF.Material and Method We established a beagle model with TEF by punching the trachea and esophagus membrane and suturing. The beagles were divided into three groups (group 1 = 1, group 2 = 6, group 3 = 6). Group 2 and 3 received a TEF building operation. Group 3 were injected 2 ml stem cells (106 per animal), and group 2 injected saline water with same volume. Group 1 did not receive any intervention. All animals receipted total parental nutrition. The closure degree of fistula tissue was observed by bronchoscope and post-mortem after 35 d.Result Morphologic and histopathologic changes of fistulas were assessed by gross and endoscopic observation. The fistulas diameter was measured. In 35 d postoperatively, group 2 showed that 3 animals died for acute smother, 2 animal died for severe chronic pneumonia and 1 animal with consistent fistula. Group 3 showed that 2 animals fully closed, 3 animals fistula diameter significantly decreased, and 1 animal died for acute smother. In autopsy result, group 2 animals showed severer pneumonia degree than group 3 animals in 35 d.Conclusion The transplantation of stem cells can promote healing degree of TEF without any complications and relieve pneumonia at the same time.

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