P-796 Trial of Autologous Marrow derived Stem Cell Ovarian Transplantation (TAMSCOT) in young infertile women with diminished ovarian reserve for ovarian rejuvenation – HOPE still persists

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
N Singh ◽  
Y Dogra ◽  
S Mohanty ◽  
T Seth

Abstract Study question Does autologous bone marrow derived stem cell (BMDSC) ovarian transplantation optimize ovarian reserve parameters in young infertile women with diminished ovarian reserve (DOR) ? Summary answer The autologous stem cell ovarian transplantation (ASCOT) improves AFC and AMH by facilitating the recruitment of existing dormant follicles in young women with DOR. What is known already Oocyte donation is the practical therapeutic option when patients with premature ovarian ageing desire pregnancy. It involves significant psychological burden in terms of not able to have their own biological child. ASCOT has opened new doors in poor responders and premature ovarian insufficiency through its beneficial effects on ovarian reserve and IVF outcomes. However recent studies have shown contradictory results in terms of its efficacy. No prior study has been contemplated in DOR group Study design, size, duration An open label non randomized controlled trial was conducted at Division of Reproductive Medicine in collaboration with stem cell facility at tertiary care institute. Forty two infertile women less than 35 years age with DOR (AFC<5, AMH<1.2ng/ml and /or high FSH>8IU/l) were enrolled in the study during a period from January 2020 to December 2020. 20 women who did not opt for the intervention were treated as control group whereas 22 women received the intervention. Participants/materials, setting, methods Baseline hormonal profile ( Day 2 FSH, estradiol, AMH and AFC) was done in all patients. Women with abnormal uterine cavity, endometriosis, prior ovarian surgery, abnormal karyotype were excluded. Bone marrow aspiration followed by mesenchymal stem cells isolation was performed. The stem cells were transplanted in both the ovaries through transvaginal route on the same day. Follow up visits were planned at one and six months to assess ovarian reserve parameters. Main results and the role of chance The mean age, BMI and duration of infertility were comparable between the control and study group (29.5±3.34vs 29.36±2.95years, 21.51±1.40vs21.87±1.93kg/m2, 6.9±1.94vs7.04±3.67 years). The positive response in terms of improved AMH and AFC was seen in 68% (15/22) patients. The mean number of stem cells injected in these women were 77.71±25.33 million. At first follow up, there was no significant difference between mean FSH, estradiol levels and mean right and left ovarian volume (9.23±3.95 vs 9.02±3.92mIU/l, 61.46±29.25 vs 68.12±62.52 pg/ml, 2.82±2.18 vs 2.44±1.25 cc, 2.02±1.54 vs 2.72±1.06 cc, p < 0.05). There was significant increase in AMH and AFC values as compared to baseline (0.79±0.43 vs 1.26±0.82ng/ml, p = 0.03; 3.47±1.30 vs 6.40±2.23, p < 0.001). At second follow up visit, the significant increase in ovarian reserve persisted for AMH and AFC (0.79±0.43 vs 1.22±0.76 ng/ml, p = 0.02; 3.47±1.30 vs 6.93±1.71,p<0.001). There was no significant difference between serum FSH, Estradiol and ovarian volume. None of the patients developed any complication and the improvement in AFC and AMH persisted during 10 month follow up period. Limitations, reasons for caution The limitation of present study is small sample size and non randomization. However, time period for which positive effect lasts has not been documented in earlier studies. This study is currently being endeavored, and women with improved ovarian reserve are followed up for any spontaneous conception or following assisted reproduction. Wider implications of the findings The present study demonstrates beneficial role of stem cells in improving ovarian reserve parameters in women with DOR with no acquired cause. If supported by future randomized clinical studies, it could represent a paradigm shift for fertility treatment in these women providing an opportunity to have their own biological child Trial registration number CTRI/2020/01/022726

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
N Singh ◽  
Y Dogra ◽  
S Mohanty ◽  
T Seth

Abstract Study question Does autologous bone marrow derived stem cell (BMDSC) ovarian transplantation optimize ovarian reserve parameters in young infertile women with diminished ovarian reserve (DOR) ? Summary answer The autologous stem cell ovarian transplantation (ASCOT) improves AFC and AMH by facilitating the recruitment of existing dormant follicles in young women with DOR. What is known already Oocyte donation is the practical therapeutic option when patients with premature ovarian ageing desire pregnancy. It involves significant psychological burden in terms of not able to have their own biological child. ASCOT has opened new doors in poor responders and premature ovarian insufficiency through its beneficial effects on ovarian reserve and IVF outcomes. However recent studies have shown contradictory results in terms of its efficacy. No prior study has been contemplated in DOR group Study design, size, duration An open label non randomized controlled trial was conducted at Division of Reproductive Medicine in collaboration with stem cell facility at tertiary care institute. Forty two infertile women less than 35 years age with DOR (AFC<5, AMH<1.2ng/ml and /or high FSH>8IU/l) were enrolled in the study during a period from January 2020 to December 2020. 20 women who did not opt for the intervention were treated as control group whereas 22 women received the intervention. Participants/materials, setting, methods Baseline hormonal profile ( Day 2 FSH, estradiol, AMH and AFC) was done in all patients. Women with abnormal uterine cavity, endometriosis, prior ovarian surgery, abnormal karyotype were excluded. Bone marrow aspiration followed by mesenchymal stem cells isolation was performed. The stem cells were transplanted in both the ovaries through transvaginal route on the same day. Follow up visits were planned at one and six months to assess ovarian reserve parameters. Main results and the role of chance The mean age, BMI and duration of infertility were comparable between the control and study group (29.5±3.34vs29.36±2.95years, 21.51±1.40vs21.87±1.93kg/m2, 6.9±1.94vs7. 04±3.67 years) . The positive response in terms of improved AMH and AFC was seen in 68% (15/22) patients. The mean number of stem cells injected in these women were 77.71±25.33 million. At first follow up, there was no significant difference between mean FSH, estradiol levels and mean right and left ovarian volume (9.23±3.95 vs 9.02±3.92mIU/l, 61.46±29.25 vs 68.12±62.52 pg/ml, 2.82±2.18 vs 2.44±1.25 cc, 2.02±1.54 vs 2.72±1.06 cc, p < 0.05). There was significant increase in AMH and AFC values as compared to baseline (0.79±0.43 vs 1.26±0.82ng/ml, p = 0.03; 3.47±1.30 vs 6.40±2.23, p < 0.001). At second follow up visit, the significant increase in ovarian reserve persisted for AMH and AFC (0.79±0.43 vs 1.22±0.76 ng/ml, p = 0.02; 3.47±1.30 vs 6.93±1.71,p<0.001). There was no significant difference between serum FSH , Estradiol and ovarian volume. None of the patients developed any complication and the improvement in AFC and AMH persisted during 10 month follow up period. Limitations, reasons for caution The limitation of present study is small sample size and non randomization. However, time period for which positive effect lasts has not been documented in earlier studies. This study is currently being endeavored, and women with improved ovarian reserve are followed up for any spontaneous conception or following assisted reproduction. Wider implications of the findings: The present study demonstrates beneficial role of stem cells in improving ovarian reserve parameters in women with DOR with no acquired cause. If supported by future randomized clinical studies, it could represent a paradigm shift for fertility treatment in these women providing an opportunity to have their own biological child. Trial registration number CTRI/2020/01/022726


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 497.2-497
Author(s):  
J. Arroyo Palomo ◽  
M. Arce Benavente ◽  
C. Pijoan Moratalla ◽  
B. A. Blanco Cáceres ◽  
A. Rodriguez

Background:Musculoeskeletal ultrasound (MSUS) is frequently used in several rheumatology units to detect subclinical inflammation in patients with joint symptoms suspected for progression to inflammatory arthritis (IA). Synovitis grade I (EULAR-OMERACT combined score) is known to be a casual finding in healthy individuals, but studies headed to unravel its possible role on rheumatic diseases are sparse.Objectives:To investigate the correlation between synovitis grade I, and the diagnosis of IA made after a year follow-up period since MSUS findings, in patients of an MSUS-specialized unit of a Rheumatology Department.Methods:We conducted a descriptive, retrospective and unicentric study. 30 patients were selected from the MSUS-specialized unit of our Rheumatology Department from July-18 to January-19. Patients presenting synovitis grade 0 (exclusively), 2 and/or 3 on combined score were excluded. Data collection at baseline included age, sex, immunological profile and previous physical examination to the MSUS findings, as well as the diagnosis made by the rheumatologist in 1-year visit follow-up: dividing the patient sample into two groups: those who were diagnosed with IA and those not. Non-parametric statistical tests for comparing means were used.Results:The mean age was 51,6 years and 70% were females. 6 (20%) patients were diagnosed with inflammatory arthritis after a year follow-up: 2 (4,8%) psoriatic arthritis, 1 (3,3%) undifferentiated arthritis, 1 (3,3%) rheumatoid arthritis, 1 (3,3%) Sjögren’s syndrome. Non-inflammatory arthropathies were also found 24 (80%), of which, 12 (40%) were non-specific arthralgias and 8 (19%) osteoarthritis.In the group of patients who did not developed an IA the mean C-reactive protein (CPR) value was 3,12 mg/L and erythrocyte sedimentation rate (ESR) was 8,2 mm; all of them were rheumatoid factor (RF) positive and ACPA-negative except one patient. 5 (31,3%) patients presented low antinuclear antibodies (ANAs) levels. In those who HLA B-27 and Cw6 were tested (4,25%); both were negative except for one that was HLA B-27 positive. The median number of swollen and painful joint count was 0, and the mean of joints with MSUS involvement was 3,5; the mean involved metacarpophalangeal (MCP) joints was 1,83; proximal interphalangeal (PIP) joints was 1,48 and distal interphalangeal (DIP) joints 0,21.Among the group of patients that developed an IA the mean of CPR and ESR was 9,27 mg/L and 14,17 mm respectively; 2 (33%) patients were RF- positive, and 1 ACPA-positive. ANAs were positive in 3 cases (50%). The median of swollen joint count was 2 and for painful joint count was 0, the median of joints with MSUS involvement was 4,5. The mean of MSUS involvement was for MCP, PIP and DIP joints: 1,67, 2 and 0. Comparing the means of CPR values in the two groups with Student’s t-test we obtained a statistically significant difference (p=0,023). No other significant differences were found.Conclusion:Despite the limitations and possible statistical bias, the presence of MSUS-defined synovitis grade I and elevated CRP levels could be related to further diagnoses of inflammatory arthropathy. Besides, the absence of synovitis in DIP joints might have a diagnostic role. Normal physical exploration and normal levels of CRP might suggest low MSUS value. However, further research is needed to clarify the role of MSUS-defined synovitis grade I.References:[1]D’Agostino MA et al. Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce-Part 1: definition and development of a standardized, consensus-based scoring system. RMD Open. 2017;3(1):e000428.[2]Van den Berg R et al. What is the value of musculoskeletal ultrasound in patients presenting with arthralgia to predict inflammatory arthritis development? A systematic literature review. Arthritis Research & Therapy (2018) 20:228.Disclosure of Interests:None declared


Cartilage ◽  
2020 ◽  
pp. 194760352094636
Author(s):  
Yoshiharu Shimozono ◽  
John F. Dankert ◽  
John G. Kennedy

Objective To evaluate the effect of intra-articular injection of autologous micronized adipose tissue (MAT) with ankle arthroscopic debridement in patients with advanced-stage posttraumatic osteoarthritis (PTOA) of ankle. Design A retrospective cohort study investigating patients treated with arthroscopic debridement and autologous MAT injection for ankle PTOA was performed. Patients with Kellgren-Lawrence (KL) grade 3 to 4 were included. Visual analogue scale (VAS), Foot and Ankle Outcome Scores (FAOS), and patient satisfaction were evaluated. Results A total of 19 patients (19 ankles) were included (KL grade 3, 8 patients; grade 4, 11 patients). At a mean follow-up time of 14.3 months (range, 7-23 months), the mean FAOS subscales for pain and quality of life significantly increased from 48.8 and 20.1 preoperatively to 61.1 and 30.1 ( P = 0.029 and 0.048, respectively). The mean VAS score significantly improved from 6.1 to 3.8 (P = 0.003) at final follow-up. A total of 10.5% (2/19) of patients were very satisfied, 31.6% (6/19) satisfied, 26.3% (5/19) neutral, 21.1% (4/19) unsatisfied, and 10.5% (2/19) very unsatisfied with their outcomes. The overall FAOS score demonstrated a significant difference in pre- to postoperative change with 14.8 for KL grade 3 and 5.9 for KL grade 4 ( P = 0.048). Conclusions Autologous MAT injection is a safe and potentially beneficial procedure for advanced-stage ankle PTOA as an adjunct to arthroscopic debridement, although more than one-third of patients were unsatisfied with the procedure. This procedure may be more beneficial for KL grade 3 patients than grade 4 patients. However, future investigations are necessary to define the role of MAT for ankle PTOA.


2008 ◽  
Vol 396-398 ◽  
pp. 123-126
Author(s):  
Timothy Wilson ◽  
Reeta Viitala ◽  
Mervi Puska ◽  
Mika Jokinen ◽  
Risto Penttinen

The role of silica and macrophages in fibrosis is well documented, but in bone formation it is relatively unknown despite decades of research with bioactive glasses. In this study macrophages were isolated from rat peritoneal and then cultured for five days in the presence of two types of silica microparticles with different solubilities. After the fifth day the culture medium was collected, purified and used as an additive in bone marrow derived rat stem cell cultures. The stem cells were cultured for five days in α-mem containing only 0,5% of FCS, enabling cell survival but disrupting their proliferation. As controls, stem cells were also cultured in α-mem containing silica microparticles. At days one and five the amount of soluble collagen was assayed from the culture medium and the cells were counted. All stem cell cultures with macrophage medium additives were found to be proliferative, with statistically significant difference to controls. However, collagen was only produced in cultures containing medium from macrophages cultured with fast-dissolving silica microparticles. This suggests that silica can induce cell proliferation and extra cellular matrix protein secretion which is mediated by macrophages, and that the solubility of silica is also a major factor in this reaction.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4390-4390 ◽  
Author(s):  
Abhinav Deol ◽  
Judith Abrams ◽  
Ashiq Masood ◽  
Zaid Al-Kadhimi ◽  
Muneer H. Abidi ◽  
...  

Abstract Abstract 4390 Background: Plerixafor is a CXCR 4 antagonist which is now approved for use for stem cell (SC) mobilization with granulocyte colony stimulating factor (GCSF) in patients with non Hodgkin lymphoma (NHL) or multiple myeloma (MM). Prior to the approval of plerixafor, we enrolled 49 patients in a compassionate use protocol at our institution to mobilize SC for patients who previously failed at least one mobilization attempt. Methods: Patients received 0.24 mg/kg of plerixafor subcutaneously 9 –11 hrs prior to apheresis in addition to twice daily GCSF. Results: Median age of the patients was 64 years (range, 23–74 years). NHL was the most common diagnosis in 27 (55%) patients, followed by MM with 17(35%) patients and HD with 5 (10%) patients. Thirty nine patients (80%) had been treated with more than 2 chemotherapeutic regimens prior to the first attempt at stem cell collection. Thirty seven patients (76%) failed one previous mobilization attempt, while 12 (24%) had failed 2 or more previous attempts. Using the combination of Plerixafor and GCSF we collected ≥ 2.5 × 106 CD34+ cells/Kg in 33 patients (67%). The median days for pheresis were 1 day with a range of 1 to 3 days. The median SC dose collected was 4 × 106 CD34+ cells/Kg, with a range 2.5 – 14.3. The median CD-34+ peripheral blood count on the 1st day of their collection with plerixafor was 22.4/uL. In contrast the median peripheral blood CD-34+ cell count in these patients on the day of their first collection which failed was 6.2 /uL. The median increase using G-CSF and plerixafor was 14.9 CD-34+ cells/uL. We collected ≥ 2.5 × 106 CD34+ cells/Kg on 4/5 (80%) patients with HD, 13/17 (76%) patients with MM and 16/27 (59%) patients with NHL. Sixteen patients (33%) collected < 2.5 × 106 CD34+ cells/Kg. The median cell dose collected in these patients was 1.4 × 106 CD34+ cells/Kg with a range, 0.4–2.2. The median number of days of pheresis was 2 days (range, 1–4 days). In these16 patients the median CD-34+ count on the day of their previous failed collection was11.2/uL. Their CD-34+ cell count on their first day of collection after the use of G-CSF and plerixafor was 8.3/ul. Figure 1 shows the change in peripheral CD34 counts with the prior mobilization attempt and after plerixafor mobilization, for 38 patients in whom data was available. The most common side effects attributed to plerixafor were diarrhea, fatigue, thrombocytopenia and bone pain; observed in 12%, 8%, 8% and 6% patients, respectively. Forty three of the 49 patients proceeded to an autologus peripheral blood SC transplant, 34 patients received ≥ 2.5 × 106 CD34+ cells/Kg. Thirty two of these patients used the plerixafor collection as the only source of SC. Two patients had their plerixafor mobilized SC combined with a previous suboptimal SC collection. Nine patients received < 2.5 × 106 CD34 + cells/Kg; 4 patients received plerixafor mobilized SC alone, 5 patients received plerixafor mobilized SC combined with their previously mobilized SC. The preparative regimens used were R- BEAM (20 patients), Melphalan (16 patients), BEAM (6 patients) and Etoposide+TBI (1 patient). All patients received GCSF from day +6 till WBC engraftment. The median days of WBC and platelet engraftment were day +11 (range, 9–13 days) and day +16 (range, 11–77 days), respectively. There was no significant difference in days to engraftment between the patients who collected greater or less than 2.5 × 106 CD34 + cells/Kg. With a median follow up 13.7 months, long term engraftment data is available on 27 patients. The median white cell count, hemoglobin and platelet count 1 year after transplant was 4.7 × 109/L, 12.2 g/dL and 109 ×109/L, respectively. There was no significant difference in counts at the 1 year mark between patients who collected more or less than 2.5 × 106 CD34 + cells/Kg. To date 15 patients have evidence of disease progression. Two patients have developed MDS/AML post transplant. Conclusion: Overall, plerixafor leads to mobilization of sufficient stem cells in a vast majority of patients who have failed previous mobilization attempts and allows more patients to proceed to an autologous SC transplant. Plerixafor is well tolerated with minimal side effects, acceptable time to engraftment and acceptable peripheral blood counts at 1 yr after the transplant. Our analysis suggests that failure to increase peripheral CD34 count after plerixafor when compared to previous attempts may predict unsuccessful mobilization. Disclosures: Lum: Transtarget Inc: Equity Ownership, Founder of Transtarget.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5248-5248
Author(s):  
Fuyu Pei ◽  
Qi Li ◽  
Wenfeng Xu ◽  
Zhiyong Peng ◽  
Xuedong Wu ◽  
...  

Abstract Objective:To evaluate the effect of hematopoietic stem cell transplantation (HSCT) for children with leukemia in our center in recent years. Methods: We retrospectively analyzed data of 87 patients with leukemia underwent HSCT at a median age of 8 years from February 2006 to December 2013 in our center. The median follow-up time was 28 months (range, 2-96), the ratio of male to female patients was 59:28. Conditioning regimen included cyclophosphamide, fludarabine, busulfan with or without (w/o) thiotepa. Anti-thymocyte globulin and cytarabine were individually used for the patients with lymphoid leukemia and myeloid leukemia. GVHD prophylaxis included tacrolimus, mycophenolate mofetil w/o post-transplant cyclophosphamide. Median nucleated cells: 3.75 (1.16`7.56) × 107/Kg. Patients with BCR/ABL+ acute lymphoblastic leukemia (ALL) received imatinib before and after transplant over 6 months per each one. Twenty-six patients received transplant from sibling donors, 31 from haploidentical donor, 30 from unrelated donors; Status before transplant were grouped as CR1 (n= 57), CR 2 (n=13), CR 3 (n=1) and NR (n=16). Source of stem cells included PBSC in 40 cases, UCB in 3 cases, BM in 24 cases, BM+PBSC in 9 cases, and mixed stem cells (BM /PBSC+ UCB) in 11 cases. Results: The estimated 5-year overall survival (OS) was 56.8 ± 5.8% in total.Among them, OS was 54.3 ± 8.0% in 45 patients with ALL; 85.7 ± 13.2% in 8 patients with BCR/ABL+ALL; 48.6 ± 8.7% in 37 patients with BCR/ABL-ALL. 32.8 ± 15% in 29 patients with acute myeloid leukemia and 82.5 ± 11.3% in 13 patients with chronic myelogenous leukemia, respectively. Single factor analysis showed there was no significant difference for OS in comparison of BCR/ABL+ALL, BCR/ABL-ALL, AML and CML (P=0.057), but patients with BCR/ABL+ALL had higher OS compared to those with BCR/ABL-ALL (P=0.048) and to AML (P=0.040). In comparison of difference status before transplant, OS were 55.2 ± 11.6%, 54.9 ± 15.6%, 0,and 27.5 ± 11.6% in CR1, CR2, CR3 and NR, respectively (P=0.025). OS was higher in CR1 than NR (P=0.005). When comparing stem cell source, OS was 65.5 ± 8.5%, 0%, 41.7 ± 11.4%, 33.3 ± 15.7%, and 72 ± 17.8% in PBSC, unrelated CB (UCB), BM, BM+PBSC, and BM/PBSC+UCB transplants, respectively (P=0.003); PBSC transplant associated with higher OS than BM (P=0.049) and BM+PBSC (P=0.009); and BM/PBSC+UCB mixed transplant had highest OS (P=0.026). Multivariate analysis showed Risk factors for OS only remained stem cell source (P=0.046) and status before transplantation (P=0.048). the transplant types (P=0.023), and follow up time(P=0.017). Conclusion: Comparing with data reported in literature we have similar outcomesin total for childhood with leukemia. Use of imatinib pre-/post-transplant for patients with BCR/ABL+ALL conduces to the highest OS in current study. Stem cell sources and the status before transplant have a significant effect on OS. Disclosures No relevant conflicts of interest to declare.


Author(s):  
Vedamurthy Reddy Pogula ◽  
Ershad Hussain Galeti ◽  
Venkatesh Velivela ◽  
Bhargava Reddy Kanchi

Background: Treatment of the urethral strictures is challenging and with appropriate evaluation preoperatively and surgery planning it is possible to achieve good results. The objective of the study was to evaluate the efficacy of dorsal onlay buccal mucosal graft urethroplasty in treating long anterior urethral strictures.Methods: Between August 2018 to July 2019 a total of 25 patients with anterior urethral stricture were treated with dorsal onlay buccal mucosal graft urethroplasty. Age, etiology of the stricture, stricture length (≤ 7 cm, and > 7 cm), and site of the stricture were assessed as the factors affecting the success rate.Results: The clinical outcome as Success was defined as the patient not needing any form of urethral instrumentation postoperatively. The mean follow-up period was 18 months. Of 25 patients, 22 (92%) were successful and 3 (8%) were a failure. There was no statistically significant difference between the age groups, etiology of the stricture and success rate (p=0.21 and p=0.444). The statistical difference was significant for the site and length of the stricture by means of success (p=0.005 and p=0.025).Conclusions: Our results show stricture length and localization are the most important variables for good success. Because of less failure rate, single-stage dorsal onlay buccal mucosal graft urethroplasty may be offered as an alternative to staged urethroplasty in case of long urethral strictures.  


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3693-3693 ◽  
Author(s):  
YiYing Xiong ◽  
Fan Qian ◽  
Fen Huang ◽  
Yu Zhang ◽  
Yu Wang ◽  
...  

Abstract Background Engraftment failure (EF) is a formidable complication after autologous hematopoietic stem cell transplantation (auto-HSCT). Mesenchymal stem cells (MSCs) and cord blood (CB) have been found to support hematopoiesis. Thus, we designed a multicenter randomized clinical trial to investigate the effects and safety of MSCs alone or combined with CB infusion for patients with EF. Methods Twenty-two patients were randomly assigned to receive the treatment with MSCs alone (MSCs group, n=11) or MSCs combined with CB (CB group, n=11). MSCs were administered once every 2 weeks (2 doses were a cycle) in both groups, and single-unit CB was administered at the same day with the first application of MSCs in CB group; After one cycle of treatments (within 28 days), the patients who did not response to MSCs would receive the therapeutic schedule in CB group, and those patients with partial response (PR) in MSCs group and those without complete response (CR) in CB group would continue another cycle of MSCs treatment. If patients did not obtain CR after two cycles of treatments (within 56 days), they would receive other treatments including allogeneic HSCT. Results After the first treatment cycle, the effect rates were not significant difference in MSCs and CB groups (7/11 vs. 9/11, P=0.635), and the median time of hematopoietic reconstruction was 22 (18-28) and 17 (13-22) days, respectively (P=0.036) in MSCs and CB group. There was statistically significant difference regarding neutrophil engraftment, with 17 (range 9-28) and 8 (range 6-14) days respectively (P=0.030), but no difference regarding platelet engraftment, with 21 (range 18-28) and 18 (range 11-21) days respectively (P=0.092) between MSCs and CB groups. After two cycles of treatments, 17 patients obtained CR, 2 PR and 3 NR. CB chimerisms were not detected by short tandem repeat (STR) at +15 and +30 days after CB infusion. None of the patients experienced any adverse events of grade 3/4 with the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0) and acute GVHD or chronic GVHD during the period of study treatment and follow-up. One patient with PR in MSCs group and 1 NR in CB group received allogeneic HSCT at +249 and +273 days after auto-HSCT because of EF and primary disease relapse, respectively. At a median follow-up time of 345 (range 129–784) days post-transplantation, 16 patients remained alive, 3 died of relapse of primary diseases and 1 died of CMV pneumonia following allo-HSCT. None of patients developed EBV-DNA viremia and EBV-associated diseases in two groups. The 2-year overall survival, disease-free survival and tumor relapse post-transplantation were 75.2% (95% CI, 63.2-87.2%), 79.5% (95% CI, 70.1-88.9%) and 20.5% (95% CI, 11.1-29.9%) respectively. Conclusions Our data suggest that ex-vivo-expanded MSCs derived from HLA-mismatched BM alone or combined with unrelated CB are effective to EF after auto-HSCT. CB can facilitate the effect of MSCs to EF. Both two strategies do not result in GVHD or increase the risk of primary diseases relapse in patients with EF. This trial was registered at www.clinicaltrials.govas#NCT01763099. Disclosures: Liu: It was supported by 863 Program (No. 2011AA020105) and National Public Health Grand Research Foundation (Grant No. 201202017).: Research Funding; It was supported by National Natural Science Foundation of China (Grant No.81000231, No.81270647) and Science and Technology Program of Guangzhou of China (11A72121174). : Research Funding.


Author(s):  
Naivah Harharah

Objective: To compare serum Anti Müllerian Hormone (AMH) levels in infertile women with and without endometriosis, and to determine the mean levels of serum AMH in every stage of endometriosis. Method: We performed a cross-sectional study. Sixty-eight subjects who have undergone laparoscopy and fulfilled both inclusion and exclusion criteria are recruited consecutively. They are divided into two groups, namely group with endometriosis and without endometriosis. Blood samples are taken from each subject before laparoscopy, where serum AMH levels are then measured. The difference in mean levels of each group are tested with Mann-Whitney test. Result: The mean levels of serum AMH were significantly lower in the endometriosis group than those in the group without endometriosis (2.30 1.8 ng/ml vs 3.75 2.13 ng/ml; p=0.005). Using Kruskal-Wallis test, it was found that there was a statistically significant difference among endometriosis groups based on the severity of endometriosis. There was no significant difference in the mean serum AMH levels between the minimal-mild endometriosis group and without endometriosis group (p=0.34), but the mean levels of serum AMH were significantly lower in the moderate-severe endometriosis compare to the group without endometriosis (p


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
María Verónica Cuevas-Gonzalez ◽  
Álvaro Garcia-Perez ◽  
Álvaro Edgar Gonzalez-Aragon Pineda ◽  
León Francisco Espinosa-Cristobal ◽  
Alejandro Donohue-Cornejo ◽  
...  

Background. The SARS-CoV-2 virus is the cause of the latest pandemic of the 21st century; it is responsible for the development of COVID-19. Within the multiple study models for both the biology and the treatment of SARS-CoV-2, the use of stem cells has been proposed because of their ability to increase the immune response and to repair tissue. Therefore, the objective of this review is to evaluate the role of stem cells against SARS-CoV-2 and COVID-19 in order to identify their potential as a study model and as a possible therapeutic source against tissue damage caused by this virus. Therefore, the following research question was established: What is the role of stem cells in the study of SARS-CoV-2 and the treatment of COVID-19? Materials and Methods. A search was carried out in the electronic databases of PUBMED, Scopus, and ScienceDirect. The following keywords were used: “SARS-CoV-2,” “COVID-19,” and “STEM CELL,” plus independent search strategies with the Boolean operators “OR” and “AND.” The identified reports were those whose main objective was the study of stem cells in relation to SARS-CoV-2 or COVID-19. For the development of this study, the following inclusion criteria were taken into account: studies whose main objective was the study of stem cells in relation to SARS-CoV-2 or COVID-19 and clinical case studies, case reports, clinical trials, pilot studies, in vitro, or in vivo studies. For assessment of the risk of bias for in vitro studies, the SciRAP tool was used. The data collected for each type of study, clinical or in vitro, were analyzed with descriptive statistics using the SPSS V.22 program. Results. Of the total of studies included ( n = 39 ), 22 corresponded to in vitro investigations and 17 to human studies (clinical cases ( n = 9 ), case series ( n = 2 ), pilot clinical trials ( n = 5 ), clinical trials ( n = 1 )). In vitro studies that induced pluripotent stem cells were the most used ( n = 12 ), and in clinical studies, the umbilical stem cells derived were the most reported ( n = 11 ). The mean age of the study subjects was 58.3 years. After the application of stem cell therapy, the follow-up period was 8 days minimum and 90 days maximum. Discussion. The mechanism by which the virus enters the cell is through protein “S,” located on the surface of the membrane, by recognizing the ACE2 receptor located on the target cell. The evidence that the expression of ACE2 and TMPRSS2 in stem cells indicates that stem cells from bone marrow and amniotic fluid have very little expression. This shows that stem cell has a low risk of infection with SARS-CoV-2. Conclusion. The use of stem cells is a highly relevant therapeutic option. It has been shown in both in vitro studies and clinical trials that it counteracts the excessive secretion of cytokines. There are even more studies that focus on long-term follow-up; thus, the potential for major side effects can be analyzed more clearly. Finally, the ethical use of stem cells from fetal or infant origin needs to be regulated. The study was registered in PROSPERO (no. CRD42021229038). The limitations of the study were because of the methodology employed, the sample was not very large, and the follow-up period of the clinical studies was relatively short.


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