Inherited photoreceptor degenerations are not treatable diseases and a frequent cause of blindness in working ages. In this study we investigate the safety, integration and possible rescue effects of intravitreal and subretinal transplantation of adult human bone-marrow-derived mononuclear stem cells (hBM-MSCs) in two animal models of inherited photoreceptor degeneration, the P23H-1 and the Royal College of Surgeons (RCS) rat. Immunosuppression was started one day before the injection and continued through the study. The hBM-MSCs were injected in the left eyes and the animals were processed 7, 15, 30 or 60 days later. The retinas were cross-sectioned, and L- and S- cones, microglia, astrocytes and Müller cells were immunodetected. Transplantations had no local adverse effects and the CD45+ cells remained for up to 15 days forming clusters in the vitreous and/or a 2–3-cells-thick layer in the subretinal space after intravitreal or subretinal injections, respectively. We did not observe increased photoreceptor survival nor decreased microglial cell numbers in the injected left eyes. However, the injected eyes showed decreased GFAP immunoreactivity. We conclude that intravitreal or subretinal injection of hBM-MSCs in dystrophic P23H-1 and RCS rats causes a decrease in retinal gliosis but does not have photoreceptor neuroprotective effects, at least in the short term. However, this treatment may have a potential therapeutic effect that merits further investigation.

Background: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization. Methods: A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales. Discussion: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future. Trial registration: ClinicalTrials.gov NCT04466007. Registered on January 07, 2020. All items from the World Health Organization Trial Registration Data Set are included within the body of the protocol.

Background: Cell-Based Therapies (CBT) constitute a valid procedure for increasing the quantity and quality of bone in areas with an inadequate bone volume. However, safety and efficacy should be investigated prior to clinical application. The objective of this study was to evaluate the biodistribution, safety and osteogenic capacity of bone marrow-derived human mesenchymal stem cells (hBMMSCs) pre-seeded into β-tricalcium phosphate (TCP) and implanted into NOD/SCID mice at subcutaneous and intramuscular sites. Methods: hBMMSCs were isolated, characterized and then cultured in vitro on a porous β-TCP scaffold. Cell viability and attachment were analyzed and then hBMMSCs seeded constructs were surgically placed at subcutaneous and intramuscular dorsal sites into NOD/SCID mice. Acute and subchronic toxicity, cell biodistribution and efficacy were investigated. Results: There were no deaths or adverse events in treated mice during the 48-hour observation period, and no toxic response was observed in mice. In the 12-week subchronic toxicity study, no mortalities, abnormal behavioral symptoms or clinical signs were observed in the saline control mice or the hBMMSCs/β-TCP groups. Finally, our results showed the bone-forming capacity of hBMMSCs/β-TCP since immunohistochemical expression of human osteocalcin was detected from week 7. Conclusions: These results show that transplantation of hBMMSCs/β-TCP in NOD/SCID mice are safe and effective, and might be applied to human bone diseases in future clinical trials.

Chronic wounds are defined as those with disturbances in normal healing. They involve symptoms like exudate, odor, pain or impaired mobility, severely impacting life quality. In the case of patients with additional comorbidities, these are known to aggravate the healing impairment. Amniotic membrane (AM) is gaining attention for its regenerative potential, as it has shown promise in treating hard-to-heal wounds, such as diabetic foot ulcers. This work examines a series of five patients who, while suffering an array of other chronic conditions, were treated with AM for the management of non-healing chronic ulcers. Inclusion criteria involved patients with lesions that have been active at least for six weeks and resistant to multiple treatments, accompanied by complex underlying pathologies affecting cardiovascular, immune or renal functions. Exclusion criteria included untreated active infections and patients undergoing other experimental treatments. The mean age of the patients was 68.4 ± 5.2 years. Wounds were treated once a week with AM, following standardized procedures. The variables measured included pain levels, microorganism presence, wound reduction and the number of AM applications to recovery. The median pain VAS score decreased significantly from seven at the start to two at the end of procedures. Four out of five patients achieved complete epithelialization, while the remaining patient showed significant reductions of 40% in wound size after 14 months. Our results confirm how the application of AM is a safe and effective resource for the management of chronic wounds in patients with serious comorbidities, enhancing patients’ quality of life, firstly by reducing pain, later by allowing recovery. Future research, including molecular analyses of wound exudates before and after AM treatment, can contribute to better understanding and fine tuning of this therapeutic resource.