Expansion of human mesenchymal stem/stromal cells (hMSCs) in bioreactors using microcarriers: lessons learnt and what the future holds.

Human mesenchymal stem/stromal cells (hMSCs) present a key therapeutic cellular intervention for use in cell and gene therapy (CGT) applications due to their immunomodulatory properties and multi-differentiation capability. Some of the indications where hMSCs have demonstrated pre-clinical or clinical efficacy to improve outcomes are cartilage repair, acute myocardial infarction, graft versus host disease, Crohn's disease and arthritis. The current engineering challenge is to produce hMSCs at an affordable price and at a commercially-relevant scale whilst minimising process variability and manual, human operations. By employing bioreactors and microcarriers (due to the adherent nature of hMSCs), it is expected that production costs would decrease due to improved process monitoring and control leading to better consistency and process efficiency, and enabling economies of scale. This approach will result in off the shelf (allogeneic) hMSC-based products becoming more accessible and affordable. Importantly, cell quality, including potency, must be maintained during the bioreactor manufacturing process. This review aims to examine the various factors to be considered when developing a hMSC manufacturing process using microcarriers and bioreactors and their potential impact on the final product. As concluding remarks, gaps in the current literature and potential future areas of research are also discussed.

[Unusual neoplasm in the scrotum].

A clinical case of scrotal atavism in the form of bone plate, which simulated neoplasm of scrotal organs and has not been previously described, is presented in the article. In our opinion, the tumor is a vestige of Bakulyum, an organ, which disappeared in Homo sapiens. The patient was successfully operated in the outpatient surgical department with good functional and long-term results. After 1-year follow-up, there were no complaints or recurrence. The patient had normal sexual function.

[Varicocele in second adulthood and elderly men].

The prevalence ofvaricocele in second adulthood and elderly men was evaluated. It was found that varicocele in this age group occurs in 15.8 % of cases , whereas in men up to 35 years - in 18.3 % of cases. 88.5 % of men older than 35 years had children. Varicocele is often asymptomatic. The course of varicocele includes compensation and decompensation stages. Proportion of adulthood and elderly patients with decompensated stage ofvaricocele in the structure ofurological disease was 0.34 %. Pain is the main manifestation of varicocele at the stage of decompensation in second adulthood and elderly men. For surgical correction of varicocele in such patients, Sayfan technique seems appropriate, which uses transinguinal mini assess (2.5-3 cm incision) allowing to identify and eliminate most of the possible causes of pain: infantile hernia, benign tumors of adipose tissue, fibrotic changes in the tissues along the ilioinguinal nerve. This minimally invasive technique can be used in outpatient surgery. 18 patients underwent surgery using this technique. There were no early postoperative and long-term complications. At 1 to 3 years after surgery, 13 patients were re-examined, and relapses were not revealed.

[Influence of cell therapy and alimentary correction on the condition of microcirculatory system in experimental dyslipidemia].

A comparative analysis of the impact of cell therapy (allogenic fetal liver cells, stem cells of autologic bone marrow) on lipid homeostasis, microcirculatory disturbances and structural changes in some organs was made using the atherosclerosis model in guinea-pigs. A positive effect of cell therapy on these parameters was established. The effect was stronger and prolonged after transplantation of stem cells. Atherogenic diet weakens the effect of cell therapy. Thus, cell therapy is more effective in restriction of atherogenic risk factors.

Dyslipidogenic microangiopathy in guinea pigs at early stages of atherogenesis.

We studied the effect of dyslipidemia on lipid metabolism, state of microcirculatory system, and morphological alterations in the aorta and liver of guinea pigs at the early stages of experimental atherogenesis. The important role of microcirculatory disorders in the development of regional pathology and atherosclerosis is confirmed. The proposed alimentary model can be used in the development of novel methods for prevention and treatment of atherosclerosis.

Differentiation of bone marrow stromal stem cells into cardiomyocyte-like cells in different mammalian species.

We describe the possibility of obtaining cardiomyocyte-like cell cultures from rat, guinea pig, and human bone marrow stromal stem cells. The content of troponin I-positive cells attains 35-45% of the total number of cells in the cultures and persists at this level for up to 4 months under differentiation conditions. Spontaneous contractions of cardiomyocyte-like cells were observed after the formation of cell monolayer under differentiation conditions.