Morphological Changes in Tissue When Using Polypropylene Implants with Adsorbed Multipotent Stromal Cells in Experiment.

The subcutaneous tissue of rats after implantation of polypropylene materials with adsorbed bone marrow-derived mesenchymal multipotent stromal cells (MMSCs) was studied using light microscopy. Inflammation in response to implantation was mild, and the foreign material was encapsulated into a thin strip of dense fibrous connective tissue with multinucleated macrophages. By 1 year after introduction of the monofilament and 6 and 12 months after implantation of the mesh product, some threads were deformed, broken, and had sharp edges. Small fragments of foreign material appeared in the adjacent tissues surrounded by their own relatively thick acellular capsule. As a result of preliminary adsorption of MMSCs on polypropylene, the thickness of the connective tissue capsule decreased, its vascularization increased, and the severity of inflammatory infiltration decreased. However, all effects of MMSCs adsorption in rats were transient and disappeared within 1 week.

[Peculiarities of angiogenesis in clear cell renal cancer]. / Osobennosti angiogeneza pri svetlokletochnom rake pochki.

A literature search was conducted to review papers on the results of studies of clear cell renal cancer (CCRC) vascularization. Numerous data on the relationship between tumor pathogenesis and its vascularization have been revealed, which indicates the multifactorial nature of CCRC development and the significant role of angiogenesis in this process. It should be taken into account that patients with CCRC may have impaired vessel formation even before tumor development. To evaluate normal and pathologic angiogenesis, a pathohistologic study using immunohistochemistry is certainly necessary. Due to the significant role of angiogenesis in the development and course of CCRC, the use of drugs that suppress the formation of the vascular network in the tumor is relevant and advisable. To date, many drugs have been developed and introduced into clinical practice to inhibit angiogenesis. However, such drugs have not lived up to the expectations placed due to the frequent and rapidly developing drug resistance. Timely detection of pre-tumor and tumor processes, as well as effective treatment of cancer, including CCRC, is possible only with close cooperation between pathomorphologists and oncologists.

Possible Kidney Complications after Application of Cell Technologies for the Repair of the Resected Liver.

The state of rat kidneys after injection of bone marrow multipotent stromal cells (MSC) labeled with Vybrant CM-Dil into intact or resected liver was studied by fluorescence microscopy. The main structural changes in the kidneys after MSC injection into intact and partially resected liver manifested as granular dystrophy and necrobiotic/necrotic changes in single epithelial cells of the distal tubules and collecting ducts, thrombosis of some vessels, progression of an ascending urinary tract infection (detection of dust-like fluorescent objects), which can be due to the immunomodulating or even immunosuppressive influence of MSC and their detritus. MSC injected into the intact or resected liver, as well as the products of their degradation were not detected in the kidneys at all terms of observation. After injection of MSC into partially resected liver, manifestations of bacterial contamination of the renal medulla appeared later. The injection of MSC into the liver can be complicated by thrombosis of the renal vessels, which should be taken into account when using this administration route in the cell therapy.

Preservation of Mesenchymal Stem Cell-Derived Extracellular Vesicles after Abdominal Delivery in the Experiment.

Light luminescent microscopy was used to study the distribution of extracellular microvesicles with PKH26-stained membranes secreted by placenta-derived mesenchymal stromal cells in the uterine tissues at different terms after injections to intact rats and after abdominal delivery (a model of cesarian section). Microvesicles migrated through the uterine tissues and were detected for at least 8 days after injection. In some cases, microvesicles were more numerous in the uterus after cesarian section modeling, which can be related to blockade of microcirculation and lymph flow due to inflammation accompanying surgical intervention. The content of microvesicles in the uterine tissues gradually declined due to macrophage phagocytosis and, probably, due to their migration into the vascular bed. Despite their size, properly stained extracellular microvesicles can be detected by light microscopy in tissues after injections.

Injection of Multipotent Mesenchymal Stromal Cells as a Cause of Hemorrhages in the Regional Lymph Nodes: Experimental Study.

Hemorrhagic changes after subcutaneous injection of autologous bone marrow multipotent mesenchymal cells with transfected GFP gene and additionally stained cell membranes to WAG rats in the projection of ligated femoral vein were studied by fluorescent microscopy. Hemorrhages in tissues with experimental acute local venous occlusion were caused by a combination of venous hypertension with inflammation around the foreign body - the ligature used for ligation of the vein. Fibrin found in tissues together with erythrocytes in the hemorrhages could stimulate the formation of granulations and new vessels instead of damaged or thrombosed ones. Multipotent mesenchymal stromal cells and their detritus getting into the regional lymph nodes initiated immune reactions morphologically confirmed by stubborn hypertrophy and hyperplasia of the lymphoid nodules, hemorrhages, and manifest diapedesis of erythrocytes to the organ parenchyma and sinus system.

Some Peculiarities of Local Distribution of Multipotent Mesenchymal Stromal Cells after Their Injection into Intact Muscle Tissue in Experiment.

Changes in the muscular tissue after subcutaneous injection of autologous bone marrow multipotent mesenchymal stromal cells transfected with GFP gene and additionally stained with cell membrane dye Vybrant CM-Dil in the projection of ligated femoral vein were studied by light microscopy with luminescence. Stromal cells injected through the skin can appear not only in the damaged tissue where acceleration of regeneration processes is required, but also in intact structures located in superficial or deeper layers. In intact muscular tissue, stromal cells spreading in the perivascular tissue initiate inflammation and migration of macrophages, activate and even trigger sclerotic processes due to differentiation into connective tissue cells (fibroblasts) and stimulation of proliferation and collagen synthesis by host fibroblasts. Injected multipotent mesenchymal stromal cells are gradually phagocytized by macrophages.

Results of Experimental Ligation of the Main Vein with the Use of Cell Technologies.

Autologous multipotent mesenchymal stromal cells (MMSC) of bone marrow origin with transfected GFP gene and additionally stained cell membranes were injected to rats through the skin in the projection of ligated femoral vein. The results were evaluated by fluorescent microscopy. No signs of MMSC incorporation into the wall of ligated vessel or reorganized collaterals were detected. Angiogenesis processes involving MMSC were detected in experimental rats within just 4 days and progressed until week 2 postinjection, mainly in granulations at the site of surgical intervention and the cicatrix forming there. Injected MMSC completely formed all tunics of the new vessels and incorporated in the vessels forming from the recipient cells. MMSC and the objects created from them were gradually eliminated with participation of macrophages and replaced by structures formed from the recipient cells.

Possibility of Aggravation of Tissue Sclerosis after Injection of Multipotent Mesenchymal Stromal Cells Near the Forming Cicatrix in the Experiment.

The peculiarities of tissue sclerosis after injection of autologous bone marrow multipotent mesenchymal stromal cells transfected with GFP gene and stained with Vybrant CM-Dil cell membrane dye were studied by light microscopy with luminescence. The surgical intervention consisting in ligation of the great vein was followed by tissue sclerotic transformation caused by direct damage and chronic inflammation caused by the presence of slowly resorbed ligature. Injection of stromal cells after this intervention led to formation of more extensive scar. This can attest to the possibility of stromal cells differentiation into connective tissue cells, fibroblasts, and stimulation of proliferation and collagen synthesis by host fibroblasts. A decrease in the volume of dense fibrous connective tissue due to scar reorganization at latter terms cannot not excluded.

[Peculiarities of tissue reactions to implantation of non-degradable surgical materials].

The method of light microscopy was used to study the reactions of the surrounding tissues to the implantation of non-degradable surgical materials (prolene 3/0 thread made from polypropelene, the composite grid made from polypropelene or polyester with polylactic acid) in the subcutaneous adipose tissue of rats 1, 2, 6 and 12 months after grafting. No less than 6 rats were examined in every time point. It was shown that the tissue reactions to implantation of different non-degradable surgical materials follows the general pattern, characteristic of wound process and foreign body reaction. By the first month of observation in both groups of animals the stage of traumatic perifocal inflammation was replaced by the proliferative phase with the formation of new blood vessel and connective tissue. The tendency to reduction of the activity of productive inflammation was observed from the 1st to the 12th month together with the increased fibrous scar transformation of the granulation tissue.

Local tissue reaction to implantation of biodegradable suture materials.

Morphological changes in tissues adjacent to the implant were studied 1, 2, 6, and 12 months after implantation of biodegradable suture materials (catgut thread, DemeTECH polyfilament thread, and Surgilactin monofilament thread) into subcutaneous fat of rats. Tissue reaction to implantation of different suture materials developed as usual in response to a wound process and to a foreign body. By the end of month 1. the stage of traumatic perifocal inflammation was replaced in all groups by the proliferative phase with formation of new vessels and connective tissue. A trend to reduction of the productive inflammation activity from month 1 to month 12 was noted. Complete degeneration of the material after 12 months with complete recovery of the histoarchitecture of the adjacent tissues (restitution) was detected only after implantation of DemeTECH polyfilament thread.

[Tissue responses to silicone materials in the body].

Light microscopy was used to study connective tissue capsules formed around different silicone breast implants. It has been found that due to the activity of microfibroblasts to minimize the volume of foreign bodies, the capsule gradually shrinks; its inner surface deforms and develops an undulating appearance with a multitude of outgrowths or protrusions inside. With the passage of time, silicone migrates to the capsule tissue and outside where it is absorbed by phagocytes. The inerter to a living organism the implant material is, the less it will stimulate a macrophage response. The task of designing new implants is to search for maximally bioinert materials that are strong enough to be compressed by the capsule and be fragmented and, moreover, elastically similar to normal breast tissue.

Morphology of pararectal lymph nodes in rectal cancer after neoadjuvant therapy.

Remodeling and cytograms of pararectal lymph nodes were studied in patients with rectal cancer after neoadjuvant therapy by different protocols. Radiotherapy and its combination with chemotherapy lead to an increase in the volume of connective tissue components and significant reduction of the volume density of lymphoid follicles without germinative centers. The counts of dividing cells, immunoblasts, and plasmoblasts in various compartments of the pararectal lymph nodes changed more significantly after radiotherapy, while changes in the count of monocytes and neutrophils were more pronounced after cytostatic therapy combined with exposure to ionizing radiation. These differences can be explained by the systemic toxic effect of chemotherapeutic drugs and primarily local cytotoxic effects of radiotherapy manifesting largely at the site of exposure.

[Characteristics of changes in the axillary lymph nodes without metastases after chemotherapy in patients with mammary gland cancer].

Light microscopy of the axillary lymph nodes in 74 relatively healthy women and in 186 patients with mammary gland cancer revealed that the lymph nodes of 10.8% of the patients contained no substantia medullaris: the tractus pulposus and cerebral sinuses were replaced by various types of the connective tissue. Similar signs in the relatively healthy women were much rarer (5.4%). The frequency of the sclerotic transformation was shown to be not dependent on the neoadjuvant chemotherapy of the mammary gland cancer but increased with aging of the subjects. After the use of polychemotherapy followed by long-term traumatic surginal interventions, tissue detritus and blood formed elements were detectable in the sinus system of the regional lymph nodes.

[Changes in the aggregated lymphoid nodules and in the mesenterial lymph nodes of rats after the administration of a chemotherapeutic drug complex: response similarities and differences].

Changes in the structure and cellular composition of aggregated lymphoid nodules (ALN, Peyer's patches) of the small intestine and in mesenterial lymph nodes (MLN) were studied in 82 female Wistar rats 7, 14 and 21 days following a single intraperitoneal injection of a complex of antineoplastic drugs (cyclophosphamide, adriamycine, vincristine and prednisolone). In ALN and MLN lymphoid nodules the administration of antineoplastic drugs resulted in the decrease of the number of blast cells and mitotically dividing cells, suggesting the suppression of B-cell proliferation and differentiation. At the same time, the dimensions of germinal centers in ALN lymphoid nodules were reduced, while their mantle zone size remained unchanged. On the contrary, in MLN lymphoid nodules, mantle zone was reduced, while germinal center dimensions remained constant. Possible reasons of these differences in responses of the immune organs studied to chemotherapy, are discussed.

[Hemosiderin and siderophages in inguinal lymph nodes in chronic venous insufficiency of the legs].

Inguinal lymph nodes of patients with venous insufficiency of the lower extremities were studied by light microscopy. Presence of erythrocytes was found in all structural parts of these organs. In cortical region and paracortical zone siderophages with hemosiderin were observed. The origin of hemosiderin is discussed.

[Similarity and difference of the response of Peyer's patches and mesenteric lymph nodes of rats to polychemotherapy].

The structure of the Peyer's patches and mesenteric lymph nodes of rats at different periods after polychemotherapy was investigated by light microscopy. After the use of antitumor drugs the number of the blasts and mytoses in the lymphoid follicles with the mesenteric lymph node bright centres and in the Peyer's patch follicles lowered, that along with the decrease of the size of the mantle zone in the lymph node follicles and the decrease of the area of the bright centres in the follicles of the lympoid formations in the intestinal wall was evident of the proliferation inhibition and B cells differentiation in the lymphoid organs. After the polychemotherapy the size of the germinative centres of the Payer's patch follicles decreased while the size of the mantle zone remained unchanged. The size of the mantle zone in the follicles of the mesenteric lymph nodes decreased while the size of the germinative centres did not change. The different responses of the lymphoid organs could be associated with some remote location of the lymph nodes with respect to the antigen source (damaged epithelium and intestinal lumen contents).

[Interaction of nickelide-titanium implant with tissues in human]. / Vzaimodeistvie nikelid-titanovogo implanta s tkaniami cheloveka.

Tissues around the implant were studied at light microscopy during 3 months after formation of artificial sphincter during a reconstructive operation of anus prenaturalis. Lack of pronounced signs of inflammation and allergic reaction indicates that the above implant induces no significant pathological changes.