Deprivation of human natural killer cells and antitumor immune response

Introduction: Cell-based immunotherapy has been given increased attention as a treatment for cancer. Human natural killer (NK) cells are resident lymphocyte populations. They exhibit potent antitumor activity without human leukocyte antigen matching and without prior antigen exposure. They also are a promising tool for immunotherapy of solid and hematologic cancers. However, most cancer patients do not have enough NK cells to induce an effective antitumor immune response. This demonstrates a need for a source of NK cells that can supplement the endogenous cell population.Material and methods: In this study, we derived induced pluripotent stem cells (iPSCs) from peripheral blood T-lymphocytes using Sendai virus vectors.Results: Generated iPSCs exhibited monoclonal T cell receptors (TCR) rearrangement in their genome, a hallmark of mature terminally differentiated T cells. These iPSCs were differentiated into NK cells using a two-stage coculture system: iPSCs into hematopoietic CD34+ cells with feeder cells M210-B4 (ATCC, USA) and CD34+ cells into mature NK cells with AFT024 cells (ATCC, USA). Our results showed that iPSC-derived NK cells expressed CD56, CD16, NKp 44 and NKp 46, possessed high cytotoxic activity  and produced high level of interferon-?.Conclusion: Based on our data, derivation of NK cells from induced pluripotent stem cells should be considered in the treatment of oncologic diseases.This would allow for the development of cell therapy for cancer using immunologically compatible NK cells derived from iPSCs. This may contribute to a more efficient treatment of oncologic diseases in addition to traditional cancer treatment

Intra-articular injection of synovium-derived mesenchymal stem cells and hyaluronic acid promote regeneration of massive cartilage defects in rabbits

Introduction: The purpose of this study was to investigate whether intra-articular injection of synovium-derived mesenchymal stem cells (SD MSCs) with low molecular weight hyaluronic acid (HA) could promote regeneration of massive cartilage in rabbits.Material and methods: The SD MSCs were harvested from the knees of 10 Flemish giant rabbits, expanded in culture, and characterized. A reproducible 4-mm cylindrical defect was created in the intercondylar groove area using a kit for the mosaic chondroplasty of femoral condyle COR (De Puy, Mitek). The defect was made within the cartilage layer without destruction of subchondral bone. Two weeks after the cartilage defect, SD MSCs (2 × 106 cell/0.15 ml) were suspended in 0.5% low molecular weight HA (0.15 ml) and injected into the left knee, and HA solution (0.30 ml) alone was placed into the right knee. Cartilage regeneration in the experimental and control groups were evaluated by macroscopically and histologically at 10, 30, and 60 days.Results: On day 10, after intra-articular injection of SD MSCs, we observed an early process of cartilage regeneration in the defect area. Histological studies revealed that cartilage defect was covered by a thin layer of spindle-shaped undifferentiated cells and proliferated chodroblasts. In contrast, an injection of HA did not induce reparation of cartilage in the defect area. At 30 days, macroscopic observation showed that the size of cartilage defect after SD MSC injection was significantly smaller than after HA injection. Histological score was also better in the MSC- treated intercondylar defect. At 60 days after MSC treatment, cartilage defect was nearly nonexistent and looked similar to an intact cartilage.Conclusion: Thus, intra-articular injection of SD MSCs can adhere to the defect in the intercondylar area, and promote cartilage regeneration in rabbits

Visualization of Bonghan Microcells by Electron and Atomic Force Microscopy

*Corresponding author. Biomedical Physics Laboratory, Department of Physics, Seoul National University, Seoul 151-747, Korea. E-mail: [email protected]: The origin of adult stem cells remains an open question. If they derive from embryos, it is difficult to determine the mechanism which interrupts their differentiation during tissue formation. In the 1960s, the Bonghan microcell was suggested as one possible, yet to be described, route of stem cell production, such that they have the potential to proliferate to produce normal cells. Materials and Methods: In this study, Bonghan microcells were isolated from Bonghan tissues on rat organ surfaces, and their detailed morphology examined by electron and atomic force microscopy. Results: The ultrastructure observed distinguished them from apoptotic bodies and other microorganisms, and their unique, possible proliferation feature, as protruding threads, was imaged by atomic force microscopy

Comparison of the characteristic features of bonghan ducts, blood and lymphatic capillaries

Objective: To show that the characteristic morphological and ultrastructural features of a Bonghan corpuscle and duct presented here are consistent with the description given in the early reports of Bonghan Kim. Materials and Methods: We compared the morphological aspects of Bonghan ducts with those of blood and lymphatic capillaries on the ultrastructural level to display the manifestly distinctive nature of the Bonghan system. Results: The walls of the ductules were observed to be composed of a single layer of endothelial cells with characteristic rod-shaped nuclei and were not surrounded by a basal lamina or by accessory cells, such as pericytes or smooth muscle cells. The abluminal cell membranes of Bonghan ductules were not attached by anchoring filaments to the fibers of extracellular matrices as observed in lymphatic capillaries

Visualization of Bonghan Microcells by Electron and Atomic Force Microscopy

*Corresponding author. Biomedical Physics Laboratory, Department of Physics, Seoul National University, Seoul 151-747, Korea. E-mail: [email protected]: The origin of adult stem cells remains an open question. If they derive from embryos, it is difficult to determine the mechanism which interrupts their differentiation during tissue formation. In the 1960s, the Bonghan microcell was suggested as one possible, yet to be described, route of stem cell production, such that they have the potential to proliferate to produce normal cells. Materials and Methods: In this study, Bonghan microcells were isolated from Bonghan tissues on rat organ surfaces, and their detailed morphology examined by electron and atomic force microscopy. Results: The ultrastructure observed distinguished them from apoptotic bodies and other microorganisms, and their unique, possible proliferation feature, as protruding threads, was imaged by atomic force microscopy

Transplantation of Cultivated Fibroblasts on a Backing of Xenogenic Tissue in the Treatment of Wounds

Introduction. Trophic ulcers are a common health problem, and there are numerous treatment methods. Irreversible damage in the skin, subcutaneous tissue, and fascia with long-term ulcer existence make standard autotransplantation inneffective. Skin grafts are often complicated by partial or complete rejection of skin flaps. The aim of this study was to examine the feasibility of using transplanted cultivated allogenic fibroblasts on the backing of a cellularless xenogenic fabric for wound healing.Methods. Transplantation of cultured embryonic fibroblasts on a backing of xenogenic tissue was used in the complex treatment of trophic ulcers for stimulation of regenerative processes. Decellularization xenogenic film was previously held. Then allogenic fibroblasts were cultivated on the surface of collagen-elastin matrix. Since 2013, we treated 12 patients with giant ulcers caused by the following: lymphedema (2 patients), vascular disease (3 patients), diabetes (2 patients), after injury (4 patients), and radiation ulcer (1 patient). Dimensions of ulcers were from 150 to 600 cm2. Duration of the lower limb ulcers ranged from 8 months to 10 years. For a number of years, all patients were on a complex therapy, which had not resulted in healing wounds. During the operation when excision of granulation tissue was performed, plastic wounds perforated with the ratio 1:2 autoskin. Xenogenic fabric with cultured fibroblasts was applied on top. In this case, xenogenic film protected the skin from drying, created optimal microclimate, and cultured fibroblasts stimulating regeneration and improving engraftment.Results. The first redress was held on the fifth day. In all cases, the results of engraftment skin grafts achieved maximum possible (100%) and optimal (90%). Complete epithelialization of the cell perforation was seen in five patients on the fifth day and three on seventh day after skin plastics. Average period of inpatient treatment was 20.7 days. All patients were discharged with healed wounds.Conclusion. Thus, the treatment of trophic ulcers can be successfully solved using advances in biotechnology. Transplantation of cultivated allogenic fibroblasts on a backing of cellularless xenogenic fabric shows good clinical results due to the stimulation of regenerative processes and creates the optimum environment for autotransplants.

Paracrine regulators of colon cancer stem cells

Бағаналы ісік жасушалары аурудың емдеуден кейін қайталануының негізгі себепшісілері. Бұл клеткалармен нәтижелі күресу үшін бұл клеткалардың тірі қалу механизмдерін және оларды қоздыратын заттарды түсіну қажет. Бұл жұмыста ісік микроайналасының ісіктің өсуі мен өркендеуіне қосатын үлесі бағаланған. Бағаналы ісік клеткаларының негізгі реттеушілері ісікпен байланысқан миофибробластар мен макрофагтар және Th17 клеткалары.Раковые стволовые клетки основная причина возобновления болезни после лечения. Для эффективной борьбы с этими клетками необходимо понимание механизмов выживание этих клеток и их стимуляторов. В данной работе оценено влияние микроокружение опухоли на рост и поддержание опухоли. Основными модуляторами раковых стволовых клеток являются опухоль ассоциированные миофибробласты и макрофаги, а также Th17 клетки. Cancer stem cells are main cause of cancer recurrence. For effective treatment it is necessary to understand haw survive and stimulate these cells. In this work it was estimated influence of cancer microenvironment to growth and surveillance of cancer. The main modulators of cancer are cancer associated miofibroblasts and macrophages, and also Th17 cells

Bonghan Ducts as Possible Pathways for Cancer Metastasis

Objective: The present study has been designed to find a possible new route for the metastasis of cancer cells on the fascia surrounding tumor tissue using a novel technique of trypan blue staining. Materials and Methods: Tumor tissues were grown in the skin of nude mice after subcutaneous inoculation with human lung cancer cells. Trypan blue was recently identified as a dye with specificity for Bonghan ducts (BHDs) and not other tissues, such as blood or lymph vessels or nerves. Results: We demonstrate that the trypan blue staining technique allows the first visualization of BHDs which are connected to tumor tissues

Bonghan Ducts as Possible Pathways for Cancer Metastasis

Objective: The present study has been designed to find a possible new route for the metastasis of cancer cells on the fascia surrounding tumor tissue using a novel technique of trypan blue staining. Materials and Methods: Tumor tissues were grown in the skin of nude mice after subcutaneous inoculation with human lung cancer cells. Trypan blue was recently identified as a dye with specificity for Bonghan ducts (BHDs) and not other tissues, such as blood or lymph vessels or nerves. Results: We demonstrate that the trypan blue staining technique allows the first visualization of BHDs which are connected to tumor tissues

Synovium-Derived Mesenchymal Stem Cells in Combination with Low Molecular Weight Hyaluronic Acid for Cartilage Repair

Regeneration of damaged articular cartilage remains one of the most complex and unresolved problems in traumatology and orthopedics. In this study, we investigated whether intra-articular injection of synovium-derived mesenchymal stem cells (SD-MSCs) with low molecular weight hyaluronic acid (LMWHA) could promote the regeneration of damaged cartilage in rabbits. To answer this question, rabbits' SD-MSCs were harvested, expanded in culture, and characterized by CFU assay and a multilineage differentiation test. For in vivo study, we created a defect within the cartilage layer without destroying subchondral bone. Two weeks after the cartilage defect, SD-MSCs (2×106 cells) were suspended in 0.5% LMWHA and injected into the left knee, and hyaluronic acid (HA) solution alone was placed into the right knee. Cartilage regeneration in experimental and control groups was evaluated macroscopically and histologically at Days 30, 60, and 90. The results of the study showed an early process of cartilage regeneration in the defect area on Day 30 after intra-articular MSCs-HA injection. Histological studies revealed that cartilage defect was covered by a thin layer of spindle-shaped undifferentiated cells and proliferated chondroblasts, in contrast to a single HA injection, which did not induce cartilage regeneration. On Day 60, we observed that the size of the cartilage defect after MSCs-HA injection significantly decreased, compared to one after HA injection. On Day 90, the cartilage defect in a knee treated with MSCs-HA was fully regenerated and was similar to intact cartilage. Thus, the combined application of the MSCs, HA, and chondroinductive proteins have a high therapeutic effect on cartilage defect regeneration in rabbits