Creation of a bioartificial pancreas, including a cell-engineered construct (CEC) formed from pancreatic islets (islets of Langerhans) and a biocompatible matrix mimicking the native microenvironment of pancreatic tissue, is one of the approaches to the treatment of type 1 diabetes mellitus (T1D). Objective: to conduct preliminary in vivo studies of the functional efficacy of intraperitoneal injection of a cell-engineered pancreatic endocrine construct and a suspension of rat pancreatic islets in an experimental T1D model. Materials and methods. Tissue-specific scaffold was obtained by decellularization of human pancreatic fragments. The viability and functional activity of rat islets isolated with collagenase were determined. Experimental T1D was modeled by intraperitoneal injection of low-dose streptozotocin and incomplete Freund's adjuvant into rats. The rats were intraperitoneally injected twice with pancreatic CEC (n = 2) or islet suspension (n = 1). Glucose levels in the blood and urine of the rats were assessed. Histological examination of organs (pancreas and kidneys) of the experimental animals was carried out. Results. After the first injection, blood glucose levels gradually decreased in all animals by more than 47% of the initial values; by follow-up day 24, the glucose level rose to the initial hyperglycemic values. After repeated administration, a 63.4% decrease in glycemic level was observed in the rats with pancreatic CEC and a 47.5% decrease in the one with islet suspension. At week 5 of the experiment, blood glucose levels gradually increased in all animals. At the same time, the glycemic index of the rat with injected pancreatic CEC was 62% lower than the glycemic index of the rat with injected islets. Conclusion. Allogeneic pancreatic islets in pancreatic CEC increase the duration of stable glycemic level in T1D rats.
Introduction. The use of immunomodulators to regulate reparative processes in affected organs and tissues remains a pressing issue. Of greatest interest is liver regeneration after extended hepatic resection (EHR) in donors in right lobe living related donor liver transplantation. We propose a transdermal therapeutic system (TTS) with an immunomodulator to enhance the natural process of liver tissue regeneration. Objective: to study the effect of transdermal administration of immunomodulator sodium aminodihydrophthalazinedione on early recovery processes in the liver after EHR in in vivo experiments. Materials and methods. Sodium aminodihydrophthalazinedione was used as an active substance in TTS in the form of powder for preparation of intramuscular injection solution (Galavit®, SELVIM LLC). An experimental EHR model was performed on 22 male Wistar rats weighing 350–380 g. After HER, all animals were divided into two groups. Group 1 (n = 10) consisted of untreated animals. In group 2 (n = 12), TTS was applied immediately after liver resection. The experiment lasted for 48 hours; the TTS was changed once after 24 hours from the beginning of application. Results. In either group, there was no significant difference in the weight of liver remnant gain and in biochemical blood parameters at 48 hours after EHR. Assessment of the mitotic index (MI) of hepatocytes 48 hours after EHR revealed a significant increase in MI in both groups in comparison with the baseline (before liver resection) equal to 0.14 ± 0.07‰. The MI in group 1 and group 2 animals was 12.70 ± 4.9‰ and 17.43 ± 4.90‰, respectively (p ≤ 0.05). Conclusion. Studies on the regenerative activity of sodium aminodihydrophthalazinedione TTS on an experimental EHR model in rats showed that this drug form had a pronounced stimulating effect on the mitotic activity of liver cells.
Objective: to compare the efficiency of regenerative processes in the liver using apoptotic bone marrow-derived mononuclear cells (BMMCs) and intact BMMCs from healthy animals on an extended liver resection (ELR) model. Materials and methods. Male Wistar rats (n = 77) with an ELR model (70–75%) were divided into 3 groups: group 1 (control with a single intraperitoneal injection of saline), group 2 (single intraperitoneal injection of unsorted intact BMMCs at a dose of 30–35 × 106, and group 3 (single intraperitoneal injection of apoptotic BMMCs at the same dose). Restoration of biochemical parameters of liver function and mass, as well as the emerging microstructural changes in hepatocytes in histological preparations, were monitored by assessing hepatocyte mitotic activity (MA) during the first 7–10 days after ELR. Results. It was found that in groups 2 and 3, as compared with group 1, there was no death after ELR modeling, and that the biochemical parameters of liver function normalized more rapidly (at days 10–14). Hepatocyte MA in group 3 sharply increased as early as on day 1, and mitotic index (MI) averaged 14‰, reaching 20.9‰ in some experiments; MI in the control group remained at the baseline by this time, while in group 2, MI was only 3.2‰. In group 3, liver mass recovered more rapidly after ELR to baseline values already at days 8–10, whereas the recovery was at day 12–14 and day 17–20 in group 2 and group 1, respectively. It was suggested that the more pronounced increase in the efficiency of regenerative processes in the liver after ELR in group 3 after using apoptotic BMMCs was due to the release from these cells of a large spectrum of formed paracrine factors, including various classes of RNA molecules involved in the regeneration process. Conclusion. Apoptotic BMMNCs have a more effective adaptive and regulatory potential than intact BMMCs because reorganizations are rapidly formed in the damaged liver cells, providing an early and more powerful activation of the targeted regenerative program.
Cell death represents the most critical pathologic entity in liver disease, which dictates pathologic consequences such as inflammation, fibrosis, and cell transformation. We analyzed the conclusions of studies on the involvement of different types of programmed cell death (PCD) in the pathogenesis of liver diseases. Three main forms of PCD (autophagy, apoptosis, necrosis) and five additional, still insufficiently studied PCD – necroptosis, ferroptosis, pyroptosis, partanatosis and entosis – observed in the liver in various acute and chronic diseases are considered. The involvement of several PCD at once in the development of any one pathology and one type of PCD in different pathologies was established. This indicates the existence of cross-regulation of metabolism in the liver cells with different levels of damage in the formation of the main dominant type of PCD. Available results indicate the possibility of attenuation (correction) of functional and morphological manifestations of PCD in the organ by controlled blocking of effector-mediated PCD pathways, as well as targeted induction of autophagy, anti-apoptotic and anti-necrotic mechanisms in liver cells.
Background. As scientific knowledge about the peculiarities of the structure and functional properties of the skin increased, it became clearer that during transdermal administration, drug may accumulate in the deep layers of the dermis and subsequently get diffused into the bloodstream even after the transdermal therapeutic system (TTS), also called transdermal patch, had been removed. Objective: to quantify active drug substances remaining in an animal skin after TTS application. Materials and methods. Two previously developed transdermal patches containing Russian-made drug substances were chosen for the study: aminodihydrophthalazinedione sodium (immunomodulator) and bis(1-vinylimidazole-N) zinc diacetate (antidote for carbon monoxide). The study was performed on male Chinchilla rabbits weighing 2.5–3 kg. Five series of experiments were performed for each substance: immediately after removal of the patch, 4 hours later, at week 1, 2 and 3 after removal. High-performance liquid chromatography and atomic absorption spectroscopy methods were used to quantify residual drug substances left in the skin. Results. In the skin flap that was in contact with the aminodihydrophthalazinedione sodium TTS for 24 hours, 0.516 mg of the drug was detected immediately after removal of the patch. Over the next two weeks, the drug substance in the skin decreased with the immunomodulator significantly reducing to 0.41 mg in the first 4 hours. In the skin flap that had been in contact with zinc bis(1-vinylimidazole-N) diacetate for 24 hours, about 1 mg of the drug was present immediately after patch removal. Four hours after removal of the transdermal patch, the quantity of active substance in the skin remained practically unchanged. At week 1 and 2, the quantity of the antidote decreased slightly to ~0.7 mg and ~0.25 mg, respectively. Conclusion. For transdermal application of aminodihydrophthalazinedione sodium, the skin can act as a drug depot and prolong the effect of this drug even after the transdermal patch had been removed. No such effect was found in the case of bis(1-vinylimidazole-N) zinc diacetate, which is apparently due to the different solubility of the drugs in the biotissue.
Introduction. Immunomodulator Galavit® is a promising domestic drug for the prevention and treatment of various infectious diseases. Earlier, the authors have developed and investigated in vitro its new dosage form – transdermal therapeutic system (TTS). Positive results from experiments made it possible to proceed to the study of the pharmacokinetic parameters of Galavit® TTS in animals.Objective: to compare the pharmacokinetic parameters of intramuscular and transdermal administration of immunomodulator Galavit® in animal experiments.Materials and methods. Sodium aminodihydrophthalazinedione was used as a substance in the form of a powder to prepare a solution for intramuscular administration of 100 mg (trade name Galavit®, manufacturer SELVIM LLC). The pharmacokinetics of transdermal and intramuscular injections were studied in male Chinchilla rabbits weighing 4.5–5.0 kg. Serum sodium aminodihydrophthalazinedione concentrations in animals were determined by highperformance liquid chromatography using a specially developed technique.Results. In contrast to the injection method, a prolonged and uniform inflow of the drug substance (MP) into the body is observed for percutaneous administration of sodium aminodihydrophthalazinedione. The maximum serum Galavit® concentration for a 40 mg dose (0.172 ± 0.054 μg/mL) and for a 80 mg dose (1.16 ± 0.22 μg/mL) remained at a constant level for 9 and 8 hours, respectively. The relative bioavailability of the Galavit® transdermal therapeutic system was 0.65 and 1.06 for the same doses.Conclusion. Application of Galavit® 80 mg transdermal therapeutic system provides bioavailability that is similar to the intramuscular administration of this drug at the same dose. At the same time, its maximum serum concentration significantly decreases and the retention time of Galavit® in the body increases by more than 10 times, which can contribute to prolongation of the drug effect. Due to the current growing interest in the use of immunomodulator Galavit® for coronavirus infection COVID-19, the development and study of a new dosage form is a promising task
Objective : to study the peculiarities of the induction effect of total RNA (tRNA) from xenogenic bone marrow cells (BMCs) on regeneration processes in the recipient's native liver with extensive liver resection using an adoptive transfer model. Materials and methods . The study was carried out on an adoptive transfer model using male Wistar rats (n = 20) and guinea pigs (n = 17). The donors were rats (n = 10). 12 hours after extensive liver resection (70-75%), tRNA was isolated from BMCs and injected into intact (non-operated) recipients intraperitoneally at a dose of 30 μg/100 g of weight. The induction effect of the tRNA on operated rats was studied in 3 groups of recipients: Group 1 (control, n = 5) - administration of saline to guinea pigs; Group 2 (control, n = 10) - administration of tRNA from a donor rat to a recipient rat (allogeneic transfer); Group 3 (experiment, n = 12) - administration of tRNA from a donor rat to a recipient guinea pig (xenogeneic transfer). In histological preparations of recipient livers, after 48, 72 hours and 7 days, we studied the mitotic activity of hepatocytes and the features of the microscopic picture of the liver. The significance of differences in the compared groups was assessed using the parametric Student's t-test. Results. The ability of BMC tRNA to tissue-specifically activate regenerative and immune responses in the liver after extensive resection was found to depend on the donor and recipient species identity. Introduction of allogeneic donor tRNA in the recipient's liver resulted in predominant enhancement in hepatocyte mitotic activity (p < 0.05). The use of xenogeneic donor tRNA leads to enhanced activity of only immuno-inflammatory reactions in the recipient's liver, such as sinusoidal cell activation, lymphocytic infiltration into sinusoids, and portal tract infiltration by inflammatory cells. Conclusion. To induce regenerative processes in the liver, tRNA obtained from allogeneic BMCs should be used.
Objective: using an adoptive transfer model to study the cellular mechanisms involved in the formation of the initial stage of liver regeneration during intraperitoneal injection of a healthy recipient with apoptotic bone marrowderived mononuclear cells (BM-MNCs) from a donor after extended liver resection.Materials and methods. Male Wistar rats (n = 40) were used to create a model of adoptive transfer of apoptotic BM-MNCs (a-BM-MNCs) taken from the donor after extended liver resection to a healthy recipient. During the experiments, the animals were divided into five groups. Four experimental groups with intraperitoneal injection of the same doses to the recipient: freshly isolated BM-MNCs (group 1); BM-MNCs subjected to apoptosis for 48 hours by storage at t = 4–6 °C in phosphate-buffered saline (PBS) (group 2) or in a Custodiol HTK solution (group 3). In group 4, the animals were injected with PBS after storing BM-MNCs in it. The control animals were animals injected with saline (group 5). For selection of effective modes of apoptosis induction, BM-MNCs stained with 7AAD after incubation in solutions were analyzed by flow cytometry. Targeted transfer of regenerative signals to the recipient was assessed by the mitotic activity of hepatocytes in the liver and tubular epithelium in the kidneys, as well as by the intensity of microstructural changes in the liver 24, 48 and 72 hours after injection of the studied material.Results. BMC incubation in PBS and HTK for 48 hours at t = 4–6 °C provides the most effective accumulation of a-BM-MNCs in early apoptosis. It was shown that a-BM-MNCs retain the ability to target-focused transmission of regulatory signals to the liver supported by autophagy process during adoptive transfer. It was established that a-BM-MNCs (groups 2 and 3) in comparison to native BM-MNCs (group 1) at adoptive transfer increased the regenerative potential of the liver due to pronounced increase in the activity of autophagy processes and directed infiltration of immunomodulatory mononuclear cells in the liver.Conclusion. a-BM-MNCs create a stronger basis for development and implementation of a targeted and effective regeneration program by enhancing autophagy processes and immunomodulatory effect on mononuclear cells, which are regenerative signal carriers.
Objective: to study the cellular mechanisms of activation of regenerative processes in the liver when using total RNA (tRNA) of bone marrow cells (BMCs) based on an extended liver resection (ELR) model. Materials and methods. Male Wistar rats (n = 80) with ELR model (70%) were divided into 2 groups: group 1 (control group) had a single saline injection, while group 2 (experimental group) received a single tRNA injection at a 30 μg/100 g dose of animal weight. The biochemical parameters of liver function and weight were monitored over time. Also monitored were microstructural changes in hepatocytes 48 hours after ELR by examining mitotic activity, caspase-9 expression and morphometric parameters. Results. It was found that in group 2, in comparison to group 1, there was faster normalization of biochemical parameters (by 10–14 days), a higher mitotic index of hepatocytes (23.45‰ versus 5.37‰), and initially sharper decrease and then faster recovery of liver mass (by 10–12 days versus 18–20 days). Both groups showed almost total expression of caspase-9, including in mitotically splitting hepatocytes. Group 1 demonstrated decreased values of morphometric parameters of single and binuclear cells, decreased number of binucleated hepatocytes and increased total density of hepatocytes as compared to the intact liver. Intraperitoneal administration of tRNA increased morphometric parameters of mononuclear hepatocytes, did not affect their number, but increased the area of the nuclei of binuclear hepatocytes as compared to the control group. Conclusion. The proven capability of cell-bone marrow total RNA to simultaneously support apoptosis in liver cells after ELR and induce mitotic activity indicates that tRNA can switch activated apoptosis to cell proliferation at the early phase of the regenerative process. This effect may be due to the presence of regulatory RNA molecules in tRNA, including numerous non-coding RNAs.
Objective: to study the cellular mechanisms of activation of regenerative processes in the liver when using total RNA (tRNA) of bone marrow cells (BMCs) based on an extended liver resection (ELR) model. Materials and methods. Male Wistar rats (n = 80) with ELR model (70%) were divided into 2 groups: group 1 (control group) had a single saline injection, while group 2 (experimental group) received a single tRNA injection at a 30 μg/100 g dose of animal weight. The biochemical parameters of liver function and weight were monitored over time. Also monitored were microstructural changes in hepatocytes 48 hours after ELR by examining mitotic activity, caspase-9 expression and morphometric parameters. Results. It was found that in group 2, in comparison to group 1, there was faster normalization of biochemical parameters (by 10–14 days), a higher mitotic index of hepatocytes (23.45‰ versus 5.37‰), and initially sharper decrease and then faster recovery of liver mass (by 10–12 days versus 18–20 days). Both groups showed almost total expression of caspase-9, including in mitotically splitting hepatocytes. Group 1 demonstrated decreased values of morphometric parameters of single and binuclear cells, decreased number of binucleated hepatocytes and increased total density of hepatocytes as compared to the intact liver. Intraperitoneal administration of tRNA increased morphometric parameters of mononuclear hepatocytes, did not affect their number, but increased the area of the nuclei of binuclear hepatocytes as compared to the control group. Conclusion. The proven capability of cell-bone marrow total RNA to simultaneously support apoptosis in liver cells after ELR and induce mitotic activity indicates that tRNA can switch activated apoptosis to cell proliferation at the early phase of the regenerative process. This effect may be due to the presence of regulatory RNA molecules in tRNA, including numerous non-coding RNAs.
Aim: to carry out a comparative assessment of the effectiveness of recovery processes in the liver after modeling of chronic fibrotic liver damage (CFLD) at using of bone marrow mononuclear cells (BMMC) and total RNA (tRNA), isolated from BMMC. Materials and methods. In this study it was used 140 rats of Wistar breed. CFLD was modeled on 100 rats, of which 25 died. The surviving 75 rats (CFLD formed by 3 months) were divided into 3 groups: group 1 - control (administration of saline solution); group 2 - single administration of tRNA from BMMC at a dose of 30 mu g/100 g weight; group 3 - single administration of BMMC at a dose of (30-35) x 10(6) cells. The dynamics of recovery processes in the liver was evaluated by the mortality of animals, as well as by the dynamics of the recovery of biochemical parameters (A1AT, MAT, ALP and total protein) and morphological status of the liver in 7 days and in 3,6 and 9 months. The reliability of differences between compared values was evaluated by the t - Student criterion at p < 0.05. Results. The mortality of animals with CFLD in group 1 was 12%, in groups 2 and 3 by 4%; In group 1- A1AT and AsAT were restored to normal values in 2 months, ALP in 3 months, and the total protein remained reduced for more than 4 months. In groups 2 and 3, all hepatic homeostasis indices returned to the values, which were before CFLD modeling, faster than in group 1 (in 2 months), but in group 2 the recovery rate was higher than in group 3. It was shown that the normalization of liver functional parameters in all groups was ahead of the restoration of its histological structure. The activation of liver defibrotic processes in group 2 occurred in 3 months, and in groups 1 and 3 - in 6 months. The restoration of liver histological structures in group 2 occurred in 6 months, and in groups 1 and 3 - after 9 months. Conclusion. BMMC and tRNA from BMMC in biologically effective doses take in part at the activation of liver recovery processes after modeling CFLD, but the regulatory impact of tRNA appears earlier and is more effective.
Aim: to conduct a comparative assessment of the effectiveness of liver regeneration occurring after induction of chronic fibrosing liver disease (CFLD) using bone marrow mononuclear cells (BMMCs) and total RNA (tRNA) extracted from BMMCs.Materials and methods. The study involved 140 Wistar rats. CFLD was modeled in 100 rats, of which 25 died. The surviving 75 rats (CFLD formed by the third month) were divided into 3 groups: Group 1 – control (administered with physiological saline); Group 2 – a single injection of tRNA from BMMCs at a dose of 30 μg/100g body weight; Group 3 – a single injection of BMMCs at a dose of (30–35) × 106 cells. The dynamics of regenerative processes in the liver was evaluated based on the animal mortality, dynamics of restoration of biochemical markers (ALAT, ASAT, alkaline phosphatase and total protein) and morphological picture of the liver on the seventh day and after three, six and nine months. The significance of differences in the compared values was determined through Student’s t-test for <0.05.Results. Mortality in Group 1 was 12%, in Groups 2 and 3 – 4%; In Group 1, ALAT and ASAT were restored to normal values after two months, alkaline phosphatase after 3 months, and total protein remained low for over 4 months. In Groups 2 and 3, all hepatic homeostasis markers returned to the values they were before CFLD modeling faster than in Group 1 (after two months). However, in Group 2, the regeneration rate was higher than in Group 3. It was revealed that normalization of functional liver parameters in all groups were ahead of restoration of the histological structure of the liver. Liver defibrotic processes in Group 2 were activated after 3 months, and in Groups 1 and 3 – after 6 months. The histological structure of the liver was restored in Group 2 after 6 months, and in Groups 1 and 3 after 9 months.Conclusion. BMMCs and tRNA extracted from them in biologically effective doses trigger liver regeneration in CFLD. However, regulatory effect from the use of tRNA appears earlier and is more effective.
Extensive liver resection (ELR), performed in a number of surgical operations, refers to a critical injury, which necessitates the improvement of methods of therapy of acute post-resection liver failure.Aim:to compare the effectiveness of stimulation of regenerative processes in the liver residue after ELR (60–70%) by intraperitoneal administration of lysed aspirate bone marrow cells (BMCs) and total RNA (tRNA) isolated from BMCs.Materials and methods.This work was performed on 175 rats-male Wistar breed 250–300 g, on 75 of which under the inhalation anesthesia it was reproduced the model of the ELR in three groups of experiments: group 1 – control (administration of isotonic solution after ELR), group 2 – in 3–5 hours after ELR the tRNA from BMCs was intraperitoneally injected at a dose of 30 μg/100 g, group 3 – in 3–5 hours after ELR BMCs was administered intraperitoneally at a dose of 30–35 × 106cells per rat. Comparative studies of the restorative processes in the liver after the ELR in the three groups were carried out by dynamic control of the mitotic activity of hepatocytes in the liver residue, cytolytic enzymes, total bilirubin and total serum protein, as well as the liver residue (mass) weight.Results.The tRNA from BMCs and BMCs in the indicated doses prevent the risk of the development of lethal outcomes, and also contribute to an earlier (by 10–14 days) normalization of the functional indices of hepatic homeostasis. However, the tRNA from BMCs, compared with BMCs, has a stronger stimulating effect on the recovery processes: it promotes earlier intensification of mitotic activity of hepatocytes and provides a higher rate of recovery of liver mass.Conclusion.For the induction of recovery processes in the liver residue after ELR, the preference should be given to the tRNA from BMCs.
Aim : to conduct a comparative assessment of the effectiveness of liver regeneration occurring after induction of chronic fibrosing liver disease (CFLD) using bone marrow mononuclear cells (BMMCs) and total RNA (tRNA) extracted from BMMCs. Materials and methods . The study involved 140 Wistar rats. CFLD was modeled in 100 rats, of which 25 died. The surviving 75 rats (CFLD formed by the third month) were divided into 3 groups: Group 1 – control (administered with physiological saline); Group 2 – a single injection of tRNA from BMMCs at a dose of 30 μg/100g body weight; Group 3 – a single injection of BMMCs at a dose of (30–35) × 106 cells. The dynamics of regenerative processes in the liver was evaluated based on the animal mortality, dynamics of restoration of biochemical markers (ALAT, ASAT, alkaline phosphatase and total protein) and morphological picture of the liver on the seventh day and after three, six and nine months. The significance of differences in the compared values was determined through Student’s t-test for <0.05. Results . Mortality in Group 1 was 12%, in Groups 2 and 3 – 4%; In Group 1, ALAT and ASAT were restored to normal values after two months, alkaline phosphatase after 3 months, and total protein remained low for over 4 months. In Groups 2 and 3, all hepatic homeostasis markers returned to the values they were before CFLD modeling faster than in Group 1 (after two months). However, in Group 2, the regeneration rate was higher than in Group 3. It was revealed that normalization of functional liver parameters in all groups were ahead of restoration of the histological structure of the liver. Liver defibrotic processes in Group 2 were activated after 3 months, and in Groups 1 and 3 – after 6 months. The histological structure of the liver was restored in Group 2 after 6 months, and in Groups 1 and 3 after 9 months. Conclusion . BMMCs and tRNA extracted from them in biologically effective doses trigger liver regeneration in CFLD. However, regulatory effect from the use of tRNA appears earlier and is more effective.
Aim. To establish the ability of the total RNA extracted from the body’s bone marrow cells (BMCs), in which liver tissue was damaged, to serve as a carrier of targeted regenerative signals to this organ.Materials and methods. By method of adoptive transfer in rats (n = 37) the mitotic and proliferative activity of liver and kidney cells were studied in intact recipients after intraperitoneal injection: the mononuclear BMCs – 2,5×106; 5,0×106; 3,5×107 cells – group 1 and the total RNA of the same BMCs (30μg/100g of weight) – group 2 from donors in 12 hours after 70–75% of hepatectomy; in group 3 (control), a saline solution was injected. RNA from BMCs was extracted by the method developed by the «Evrogen» firm (Russia) with the reagent Extract RNA.Results. In group 2 in 48 and 72 h. there was the increasing of mitotic and proliferative cell activity in the liver, but not in the kidneys (control of the specificity of regenerative signals); in group 1 there was no transfer of regenerative signals to these organs.Conclusion. The authors believe that the total RNA from BMCs, activated by hepatectomy, accumulates targeted (hepatospecific) regeneration signals, but they are perceived only when RNA has been obtained by the damaged tissue.
Aim. To research the rat bone marrow mesenchymal stem cells (MSC BM) effect to the viability of isolated rat OL during cultivation with microstructured collagen-containing hydrogel (BMCH). Materials and methods. Rat islets and MSC BM were isolated according to classical technique with some modifications. The experiments on the co-cultivation were carried out under standard conditions. Islet's viability was determined by immunofluorescence staining. Results. TheOL cultivation with BMCH and MSCBM resulted in destructive changes of isletson the third day, and complete destruction of OL was observed on the seventh day. At the same time, OL cultured with BMCH remained viable for 14 days of incubation. Conclusion. Cultivation of OL with BMCH and MSC BM did not contribute to the long-term survival of the islets. Thus, there was no positive effect of MSC BM on the viability of pancreatic islets.