BACKGROUND:Recently we reported results of phase 1 pilot clinical trial of 2 consecutive intracavernous (IC) injection of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) for the first time in the treatment of diabetic patients with erectile dysfunction (DM-ED). In phase 2 of this study our aim is to evaluate long term safety and efficacy of IC injections of BM-MSC on additional eight patients with DM-ED. RESULTS:Each patient received 2 consecutive IC injections of BM-MSC and evaluated at 1, 3, 6, 12, and 24-month time points. Primary outcome was the tolerability and safety of stem cells therapy (SCT), while the secondary outcome was improvement of erectile function (EF) as assessed using the International Index of Erectile Function-5 (IIEF-5), Erection Hardness Score (EHS) questionnaires, and Color Duplex Doppler Ultrasound (CDDU). IC injections of BM-MSCs was safe and well-tolerated. Minor local and short-term adverse events related to the bone marrow aspiration and IC injections were observed and treated conservatively. There were significant improvement in mean IIEF-5, EHS, all over the follow-up time points in comparison to the baseline. At 24-month follow up there were significant decline in the mean IIEF-5, and EHS compared to the baseline. The mean basal and 20-min peak systolic velocity was significantly higher at 3-month after the IC injections compared to baseline. CONCLUSIONS:This phase 2 clinical trial confirmed that IC injections of BM-MSC are safe and improve EF. The decline in EF over time suggests a need for assessing repeated injections. CLINICAL TRIAL REGISTRATION:NCT02945462.

ABSTRACT Mesenchymal stem cells (MSCs) are used as novel therapeutic tools in cell-based therapies including diabetic complications. However, diabetes may negatively affect the therapeutic potential of autologous MSCs. In order to enhance the utilization of diabetic MSCs, better characterization of their angiogenic capacity should be performed. The aim of this study was to investigate the effect of diabetes mellitus (DM) on the angiogenic potential of bone marrow derived MSCs. MSCs were isolated from DM subjects and were compared with MSCs isolated from non-DM subjects. The angiogenic potential of MSCs was assessed in which there was insignificant difference in the proliferation and expression of angiogenic factors between the two groups. Moreover, no statistically significant change was found in the viability and angiogenic activities of endothelial cells isolated from both groups. Results indicate that the hyperglycemic milieu had no significant impact on the angiogenic-related functional properties of MSCs and they are able to survive the harsh diabetic conditions.

Diabetes Mellitus Type 1 is an autoimmune disease that occurs due to the destruction of insulin-producing cells (β cells), resulting in hyperglycemia. Therefore, diabetic patients depend on insulin treatment for the rest of their lives. Stem cells are considered a promising cellular therapy to replace the nonfunctional beta cells with functional and mature beta cells. Hence, in this study, we aimed to examine the potential of dental stem cells of apical papilla (SCAP) to differentiate into functional islet cell aggregates (ICAs), compared to the ICA generated from bone-marrow-derived stem cells (BM-MSCs). Our strategy was to induce the differentiation of SCAP and BM-MSCs into a definitive endoderm. The success of endodermal differentiation was determined by measuring the expression of definitive endodermal markers, FOXA2 and SOX-17, by flow cytometry. Next, the maturity and functionality of the differentiated cells were evaluated by measuring the amount of insulin and C-peptide secreted by the derived ICAs using ELISA. Additionally, the expression of mature beta cell markers-insulin, C-peptide, glucagon and PDX-1-was detected through confocal microscopy, while the staining of the mature islet-like clusters was detected by using diphenythiocarbazone (DTZ). Our results have shown that both SCAP and BM-MSCs were sequentially committed to a definitive pancreatic endoderm and β-cell-like cells by upregulating the expression of FOXA2 and SOX17 significantly (**** p < 0.0000 and *** p = 0.0001), respectively. Moreover, the identity of ICAs was confirmed by DTZ-positive staining, as well as by the expression of C-peptide, Pdx-1, insulin and glucagon at day 14. It was noted that at day 14, differentiated ICAs released insulin and C-peptides in a significant manner (* p < 0.01, *** p = 0.0001), respectively, exhibiting in vitro functionality. Our results demonstrated for the first time that SCAP could be differentiated into pancreatic cell lineage in a similar manner to BM-MSCs, suggesting a new unambiguous and nonconventional source of stem cells that could be used for stem cell therapy to treat diabetes.

The Covid-19 pandemic has changed almost all aspects of education. The anatomy and histology courses for pharmacy students focus heavily on the face-to-face communication of theory and practical knowledge, and due to the pandemic, only theory content was delivered in an online format. This brought up many concerns about pharmacy student preparedness. This work explores the effectiveness and student perspective of remote teaching of the theoretical anatomy and histology course in Jordanian universities from the perspective of pharmacy students. The objectives are to determine the strengths, challenges, and the effectiveness of remote delivery on student learning. An online-based validated questionnaire was distributed to students majoring in Pharmacy and enrolled in the course during the second semester of 2019-2020 at 11 universities in Jordan. A total of 442 students participated in the study. Results showed that there were significant differences in perceptions of the social media platforms used in distance learning and remote delivery of the course. Most participants had positive perceptions of the educational process and studying via distance learning. There were many strengths noted including time flexibility and several challenges such as the lack of face-to-face interaction with instructors, inadequate internet connectivity, and technical issues. In conclusion, online-taught anatomy and histology course during the Covid-19 lockdown in Jordan was a success as perceived by students, but the course still possessed challenges need to be overcome in the future.

Background & objectives: Platelet concentrate contains a rich cocktail of growth factors that support growth and proliferation of cells. The primary goal of this study was to investigate the safety of platelet lysate (PL) in patients with critical limb ischaemia (CLI) not suitable for standard revascularization. Data on the preliminary efficacy are also presented. Methods: Seven patients (18-70 yr) with CLI classified in the Rutherford grades 3-5, with history of intermittent claudication for more than eight weeks and were not suitable for standard revascularization, underwent autologous intramuscular injections of PL. These patients were examined physically alongside other parameters such as TcPO2, toe pressure, and ankle brachial index, at baseline and were followed up for 12 months. Results: The procedure was well tolerated with no serious adverse or any adverse events reported during follow up. Although not the primary aim of this report, preliminary data showed significant clinical improvement in Rutherford stage, ankle-brachial index and toe pressure which persisted for a year. Interpretation & conclusions: Intramuscular injection of PL was well tolerated with no major adverse events reported in our study participants. With the observed satisfactory safety data, preliminary efficacy data of PL should be further validated.

BACKGROUND AND OBJECTIVES:Stem cell therapy is a novel treatment with regenerative ability that can treat erectile dysfunction (ED). This phase 1/2 clinical trial (NCT02945449) using 2 consecutive intracavernous (IC) injections of allogeneic Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) was studied for the first time in the treatment of diabetic patients with ED. The primary outcome was to assess the safety and tolerability, and the secondary outcome was to assess the efficacy of 2 consecutive IC injections of allogeneic WJ-MSCs in diabetic ED.PATIENTS AND METHODS:Twenty-two diabetic patients with refractory ED were included. Two consecutive IC injections of allogeneic WJ-MSCs were performed. Tolerability was assessed immediately, and at 24 h, safety was evaluated for 12 months. Efficacy was assessed using International Index of Erectile Function-5 (IIEF-5), Erection Hardness Score (EHS), and Color Duplex Doppler Ultrasound for 12 months.RESULTS:The procedure was well-tolerated. Minimal and transient adverse events were redness and bruising at the site of injections. There were no patient-reported serious adverse effects. There were significant improvements in IIEF-5, EHS, peak systolic velocity (PSV) basal, and 20-min PSV, all over the follow-up time points in comparison to the baseline.CONCLUSION:This is the first human study with proven tolerability, safety, and efficacy of IC injections of allogeneic WJ-MSCs for the treatment of diabetic patients with ED.

Aim: Variations in the clinical outcomes using mesenchymal stem cells (MSCs) treatments exist, reflecting different origins and niches. To date, there is no consensus on the best source of MSCs most suitable to treat a specific disease. Methods: Total transcriptome analysis of human MSCs was performed. MSCs were isolated from two adult sources bone marrow, adipose tissue and two perinatal sources umbilical cord and placenta. Results: Each MSCs type possessed a unique expression pattern that reflects an advantage in terms of their potential therapeutic use. Advantages in immune modulation, neurogenesis and other aspects were found. Discussion: This study is a milestone for evidence-based choice of the type of MSCs used in the treatment of diseases.

Objectives: This open label, phase I clinical trial (NCT02945462) using 2 consecutive intracavernous autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) for the first time in the treatment of diabetic patients with erectile dysfunction (ED). The primary outcome is to assess the safety and tolerability of intracavernous autologous BM-MSCs, the secondary outcome is to assess efficacy of the procedure. Patients and Methods: Four diabetic patients with refractory ED were included. Two consecutive intracavernous autologous BM-MSC injections were performed. Tolerability was assessed immediately and at 24 h, safety was evaluated for 2years. Efficacy was assessed using International Index of Erectile Function-15 (IIEF-15) and Erection Hardness Score (EHS) for 12 months. Results: procedure was well tolerated and no patients reported significant adverse effects. There was significant improvement of IIEF-15 and EHS; IIEF-15 (p = 0.04), Erectile Function (p = 0.03), Sexual Desire (p = 0.04), Intercourse Satisfaction (p = 0.04), and Overall Satisfaction (p = 0.04). Conclusion: This is the first human study with proven tolerability, safety and efficacy of intracavernous autologous BM-MSC injections for treatment of diabetic patients with ED.