Endoscopic“calabash”ligation and resection for small gastric mesenchymal tumors

BACKGROUND Gastric mesenchymal tumors(GMT)are identified as soft tissue neoplasms that arise from mesenchymal stem cells within the gastrointestinal tract.GMT pri-marily encompass gastric stromal tumors(GST),gastric leiomyomas,and gastric schwannomas.Although most GMT are benign,there are still potential malignant changes,especially GST.Thus,early surgical intervention is the primary treat-ment for GMT.We have designed a simple endoscopic“calabash”ligation and resection(ECLR)procedure to treat GMT.Its efficacy and safety need to be com-pared with those of traditional endoscopic techniques,such as endoscopic sub-mucosal excavation(ESE).AIM To assess the safety and effectiveness of ECLR in managing small GMT(sGMT)with a maximum diameter≤20 mm by comparing to ESE.METHODS This retrospective analysis involved patients who were hospitalized in our institution between November 2021 and March 2023,underwent endoscopic resection,and received a pathological diagnosis of GMT.Cases with a tumor diameter≤20 mm were chosen and categorized into two cohorts:Study and control groups.The study group was composed of patients treated with ECLR,whereas the control group was composed of those treated with ESE.Data on general clinical characteristics(gender,age,tumor diameter,tumor growth direction,tumor pathological type,and risk grade),surgery-related information(complete tumor resection rate,operation duration,hospitalization duration,hospitalization cost,and surgical complications),and postoperative follow-up were collected for both groups.The aforementioned data were subsequently analyzed and compared.RESULTS Five hundred and eighty-nine individuals were included,with 297 cases in the control group and 292 in the study group.After propensity score matching,the final analysis incorporated 260 subjects in each cohort.The findings indicated that the study group exhibited shorter operation duration and lowered medical expenses relative to the control group.Furthermore,the study group reported less postoperative abdominal pain and had a lower incidence of intraoperative perforation and postoperative electrocoagulation syndrome than the control group.There were no substantial variations observed in other parameters among the two cohorts.CONCLUSION ECLR is a viable and effective approach for managing sGMT.

Controversies regarding transplantation of mesenchymal stem cells

Mesenchymal stem cells(MSCs)have tantalized regenerative medicine with their therapeutic potential,yet a cloud of controversies looms over their clinical tran-splantation.This comprehensive review navigates the intricate landscape of MSC controversies,drawing upon 15 years of clinical experience and research.We delve into the fundamental properties of MSCs,exploring their unique immuno-modulatory capabilities and surface markers.The heart of our inquiry lies in the controversial applications of MSC transplantation,including the perennial debate between autologous and allogeneic sources,concerns about efficacy,and lingering safety apprehensions.Moreover,we unravel the enigmatic mechanisms surro-unding MSC transplantation,such as homing,integration,and the delicate balance between differentiation and paracrine effects.We also assess the current status of clinical trials and the ever-evolving regulatory landscape.As we peer into the future,we examine emerging trends,envisioning personalized medicine and innovative delivery methods.Our review provides a balanced and informed perspective on the controversies,offering readers a clear understanding of the complexities,challenges,and potential solutions in MSC transplantation.

Interferon-gamma and tumor necrosis factor-alpha synergistically enhance the immunosuppressive capacity of human umbilical-cordderived mesenchymal stem cells by increasing PD-L1 expression

BACKGROUND The immunosuppressive capacity of mesenchymal stem cells(MSCs)is dependent on the“license”of several proinflammatory factors to express immunosuppressive factors such as programmed cell death 1 ligand 1(PD-L1),which determines the clinical therapeutic efficacy of MSCs for inflammatory or immune diseases.In MSCs,interferon-gamma(IFN-γ)is a key inducer of PD-L1 expression,which is synergistically enhanced by tumor necrosis factor-alpha(TNF-α);however,the underlying mechanism is unclear.AIM To reveal the mechanism of pretreated MSCs express high PD-L1 and explore the application of pretreated MSCs in ulcerative colitis.METHODS We assessed PD-L1 expression in human umbilical-cord-derived MSCs(hUC-MSCs)induced by IFN-γand TNF-α,alone or in combination.Additionally,we performed signal pathway inhibitor experiments as well as RNA interference experiments to elucidate the molecular mechanism by which IFN-γalone or in combination with TNF-αinduces PD-L1 expression.Moreover,we used luciferase reporter gene experiments to verify the binding sites of the transcription factors of each signal transduction pathway to the targeted gene promoters.Finally,we evaluated the immunosuppressive capacity of hUC-MSCs treated with IFN-γand TNF-αin both an in vitro mixed lymphocyte culture assay,and in vivo in mice with dextran sulfate sodium-induced acute colitis.RESULTS Our results suggest that IFN-γinduction alone upregulates PD-L1 expression in hUC-MSCs while TNF-αalone does not,and that the co-induction of IFN-γand TNF-αpromotes higher expression of PD-L1.IFN-γinduces hUCMSCs to express PD-L1,in which IFN-γactivates the JAK/STAT1 signaling pathway,up-regulates the expression of the interferon regulatory factor 1(IRF1)transcription factor,promotes the binding of IRF1 and the PD-L1 gene promoter,and finally promotes PD-L1 mRNA.Although TNF-αalone did not induce PD-L1 expression in hUCMSCs,the addition of TNF-αsignificantly enhanced IFN-γ-induced JAK/STAT1/IRF1 activation.TNF-αupregulated IFN-γreceptor expression through activation of the nuclear factor kappa-B signaling pathway,which significantly enhanced IFN-γsignaling.Finally,co-induced hUC-MSCs have a stronger inhibitory effect on lymphocyte proliferation,and significantly ameliorate weight loss,mucosal damage,inflammatory cell infiltration,and up-regulation of inflammatory factors in colitis mice.CONCLUSION Overall,our results suggest that IFN-γand TNF-αenhance both the immunosuppressive ability of hUC-MSCs and their efficacy in ulcerative colitis by synergistically inducing high expression of PD-L1.

Double-balloon enteroscopy for mesenchymal tumors of small bowel:Nine years' experience

AIM:To assess the value of double-balloon enteroscopy(DBE) for the diagnosis of gastrointestinal mesenchymal tumors(GIMTs) in the small bowel and clarify their clinical and endoscopic characteristics.METHODS:A retrospective review in a total of 783 patients who underwent a DBE procedure from January 2003 to December 2011 was conducted.Data from patients with pathologically confirmed GIMTs were analyzed at a single tertiary center with nine years' experience.The primary outcomes assessed included characteristics of patients with GIMTs,indications for DBE,overall diagnostic yield of GIMTs,endoscopic morphology,positive biopsy,comparison of diagnosis with capsule endoscopy,and subsequent interventional management.RESULTS:GIMTs were identified and analyzed in 77 patients.The mean age was 47.74 ± 14.14 years(range:20-77 years),with 63.6% being males.The majority of individuals presented with gastrointestinal bleeding,accounting for 81.8%,followed by abdominal pain,accounting for 10.4%.Small bowel pathologies were found in 71 patients,the detection rate was 92.2%.The diagnostic yield of DBE for GIMTs was 88.3%.DBE was superior to capsule endoscopy in the diagnosis of GIMTs(P = 0.006;McNemar's χ2 test).Gastrointestinal stromal tumor was the most frequent and leiomyoma was the second frequent GIMT.Single and focal lesions were typical of GIMTs,and masses with smooth or unsmooth surface were the most common in the small bowel.GIMTs were removed from all the patients surgically except one patient treated with endoscopic resection.CONCLUSION:DBE is a safe and valuable procedure for patients with suspected GIMTs,and it provides an accurate position for subsequent surgical intervention.

Esophageal mesenchymal tumors:Endoscopy,pathology and immunohistochemistry

AIM： To study the endoscopic, pathological and immunoo histochemical features of esophageal mesenchymal tumors. METHODS： Twenty-nine patients diagnosed as esophageal rnysenchymal tumors by electronic endoscopy and endoscopic ultrasound （EUS） were observed under light microscopes, and all tissues were stained by the immunohistochemical method. The expression of CD117, CD34, SMA and desmin were measured by staining intensity of cells and positive cell ratios. RESULTS： Endoscopically, esophageal gastrointestinal stromal tumors （GISTs） and leiomyomas （LMs） had similar appearances, showing submucosal protuberant lesions. They all showed low echo images originated from the muscularis propria or muscularis mucosa on EUS. Endoscopy and EUS could not exactly differentiate esophageal GISTs from LMs. Microscopically, there were two kinds of cells： spindle cell type and epitheloid cell type in esophageal GISTs. Leiomyomas and leiomyosarcornas were only of spindle cell type. One malignancy was found in five cases of esophageal GISTs, and one malignancy in 24 cases of leiomyomas and leiomyosarcomas. Using Fisher＇s exact method, the differences of malignant lesion proportion were not significant between esophageal LMs and GISTs, 1/5 vs 1/24 （P 〉 0.05）. All cases of esophageal GISTs were positive for CD117, and 3 cases were also positive for CD34. The 24 cases of leiomyomas and leiomyosarcomas were all negative for CD117 and CD34. The differences of positive rates of CD117 and CD34 were significant between esophageal GISTs and LMs, 5/5 vs 0/24, 3/5 vs 0/24 （P 〈 0.005）. All leiomyomas and leiomyosarcomas were positive for SMA, and desmin. Among 5 cases of esophageal GISTs, 2 cases were SMA positive, and 1 case was desmin positive. The differences in positive rates and expression intensity of SMA and desmin were significant between esophageal LMs and GISTs, 24/24 vs 2/5, 24/24 vs 115 （P 〈 0.005）. CONCLUSION： The most common esophageal mesenchymal tumors are leiomyomas, and esophageal GISTs are less common. Most of esophageal LMs and GISTs are benign. Endoscopy and EUS are the effective methods to diagnose esophageal mesenchymal tumors and they can provide useful information for the treatment of these tumors. However, they cannot exactly differentiate esophageal GISTs from LMs. Pathological, especially immunohistochemical features are useful to differentiate GISTs from leiomyomas.

Mesenchymal stromal cells' role in tumor microenvironment:involvement of signaling pathways

Mesenchymal stromal cells(MSCs) are adult multipotent stem cells residing as pericytes in various tissues and organs where they can differentiate into specialized cells to replace dying cells and damaged tissues. These cells are commonly found at injury sites and in tumors that are known to behave like "wounds that do not heal." In this article, we discuss the mechanisms of MSCs in migrating, homing, and repairing injured tissues. We also review a number of reports showing that tumor microenvironment triggers plasticity mechanisms in MSCs to induce malignant neoplastic tissue formation, maintenance, and chemoresistance, as well as tumor growth. The antitumor properties and therapeutic potential of MSCs are also discussed.

Evaluation of epithelial-mesenchymal transitioned circulating tumor cells in patients with resectable gastric cancer: Relevance to therapy response

AIM: To evaluate the epithelial-to-mesenchymal transition(EMT) of circulating tumor cells(CTCs) in gastric cancer patients.METHODS: We detected tumor cells for expression of four epithelial(E^+) transcripts(keratins 8, 18, and 19 and epithelial cell adhesion molecule) and two mesenchymal(M^+) transcripts(Vimentin and Twist) by a quantifiable, dual-colorimetric RNA-in situ hybridization assay. Between July 2014 and October 2014, 44 patients with gastric cancer were recruited for CTC evaluation. Blood samples were obtained from selected patients during the treatment course [before surgery, after surgery and at the 6^(th) cycle of XELOX based chemotherapy(about 6 mo postoperatively)].RESULTS: We found the EMT phenomenon in which there were a few biphenotypic E^+/M^+ cells in primary human gastric cancer specimens. Of the 44 patients, the presence of CTCs was reported in 35(79.5%) patients at baseline. Five types of cells including from exclusively E^+ CTCs to intermediate CTCs and exclusively M^+ CTCs were identified(4 patients with M^+ CTCs and 10 patients with M^+ or M^+ > E^+ CTCs). Further, a chemotherapy patient having progressive disease showed a proportional increase of mesenchymal CTCs in the post-treatment blood specimens. We used NCI-N87 cells to analyze the linearity and sensitivity of Can Patrol^(TM) system and the correlation coefficient(R^2) was 0.999.CONCLUSION: The findings suggest that the EMT phenomenon was both in a few cells of primary tumors and abundantly in CTCs from the blood of gastric cancer patients, which might be used to monitor therapy response.

Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature

Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia. Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia. The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT). Surgical removal of the responsible tumors is clinically essential for the treatment of TIO. However, identifying the responsible tumors is often difficult. Here, we report a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than three years. A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery. After complete excision of the tumor, serum FGF23 levels rapidly decreased, dropping to 54.7% of the preoperative level one hour after surgery and eventually to a little below normal. The patient's serum phosphate level rapidly improved and returned to normal level in four days. Accordingly, her clinical symptoms were greatly improved within one month after surgery. There was no sign of tumor recurrence during an 18-month period of follow-up. According to pathology, the tumor was originally diagnosed as "glomangioma" based upon a biopsy sample, "proliferative giant cell tumor of tendon sheath" based upon sections of tumor, and finally diagnosed as PMTMCT by consultation one year after surgery. In conclusion, although an extremely rare disease, clinicians and pathologists should be aware of the existence of TIO and PMTMCT, respectively.

Hepatic perivascular epithelioid cell tumors:The importance of preoperative diagnosis

Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors(PEComas)because PEComas are mainly benign tumors and may not require surgical intervention.By analyzing the causes,properties and clinical manifestations of PEComas,we summarize the challenges and solutions in the diagnosis of PEComas.

Oncogenic osteomalacia caused by a phosphaturic mesenchymal tumor of the femur: A case report

BACKGROUND Oncogenic osteomalacia caused by phosphaturic mesenchymal tumors is very difficult to detect.We report a case of tumor-induced osteomalacia caused by a phosphaturic mesenchymal tumor of the left femur in a middle-aged woman after medical imaging and biopsy.CASE SUMMARY A 57-year-old woman presented with progressive bone pain for five years.She was diagnosed with hypophosphatemic osteomalacia,as her laboratory data showed low serum phosphorus and low serum calcium.Her knee joint radiography revealed an osteolytic lesion of the left femur.A computed tomography scan showed mixed density shadows in the left femur.Magnetic resonance imaging of the left femur showed the presence of an oval area with a hypointense signal in T1-weighted magnetic resonance imaging(MRI)and highlow mixed signal in T2-weighted MRI.Biopsy samples revealed the presence of short spindle cells,vascularization,and characteristics of phosphaturic mesenchymal tumors.Tumor resection was performed,and the clinical presentations and laboratory abnormalities were reversed.CONCLUSION Diagnosis of oncogenic osteomalacia is difficult due to the varieties and localization of source tumors and absence of pathognomonic biomedical signs.Our case highlights the importance of a combination of medical imaging and biopsy in the diagnosis of oncogenic osteomalacia caused by a phosphaturic mesenchymal tumor.

Primary malignant liver mesenchymal tumor: A case report

Primary malignant liver mesenchymal tumor is a rare condition defined as a tumor with vascular, fibrous, adi-pose, and other mesenchymal tissue differentiation. We report a case of primary malignant liver mesenchymal tumor in a 51-year-old male with anemia, weight loss and hepatomegaly. Finally unconventional liver biopsy and histological manifestation led to the definitive diag-nosis.

Differentiation of Mesenchymal Stem Cells into Hepatocyte-Like Cells by Autologous Serum after Radiofrequency Ablation of Liver Tumor

Mesenchymal stem cells?(MSCs) have been shown to differentiate into liver cells in serum of part-resection liver, but it was hardly feasible in clinical use. Our studies revealed that MSCs could differentiate into hepatocyte-like cells in autologous serum after radiofrequency ablation (RFA) therapy of the liver tumor. Rabbits with liver tumor subsequently treated with RFA therapy. Serum was collected from those rabbits before RFA therapy and 72 hours after RFA therapy. MSCs were isolated from each rabbit’s bone marrow and cultured in DMEM medium containing the following different supplements: 30% fetal calf serum (FCS group), 30% rabbit autologous serum (AS group) or 30% autologous serum after RFA treatment of the liver tumor (ASRF group), observed by electron microscopy, flow cytometry, immunofluorescence. Seven days later, most of the spindle-shaped MSCs in the ASRF group transformed into polygon or round-shaped cells resembling hepatocytes, and the percentage in S/G2/M phase was higher than in the FCS or AS groups. Fourteen days later, slender microvilli, cell-cell junction structures and cholangiole emerged in the cells belonging to the ASRF group, the expression of albumin and CK18 was observed only in the differentiated cells from the ASRF group. These changes were not observed in the FCS group or the AS group. This study may provide a potential cell source and culture process for clinical application in liver injury treatment.

Oncogenic Osteomalacia Associated with Phosphaturic Mesenchymal Tumor of the Knee: Case Presentation and Review of the Literature

Oncogenic osteomalacia (OOM) is an uncommon metabolic and bone disease caused by fibroblast growth factor 23 (FGF23), a phosphaturic factor produced by phosphaturic mesenchymal tumors (mixed connective tissue variant, PMTMCTV) characterized by phosphate leakage from kidneys and subsequent hypophosphatemia. In this paper, we present the case of a patient, 42-year-old woman affected by left side limp and pain involving lumbar spine, pelvis and hip joints, referred to the Rheumatology Department of our Hospital for the treatment of a suspected sero-negative spondilo-arthritis. During hospitalization patient began an immuno-suppressive therapy with TNF-alpha inhibitors associated with Pamidornate, Indometacin, Esomeprazole and vitamin D3. Nevertheless pain did not decrease and a new examination found a worst hypophosphatemia (1 mg/dl) with normal Ca and PTH’s plasma values. During the same check-up a painful bulge on the anterior part of the right knee was observed and the Magnetic Resonance Imaging scan revealed an ovular solid lesion in the soft tissue closed to the upper part of the patella. Histological analysis identified the lesion as a PMTMCTV. After surgical removal patient got complete recovery. We will discuss about diagnostic evaluation, differential diagnosis and treatment.

Bone-marrow mesenchymal stem cells reduce rat intestinal ischemia-reperfusion injury, ZO-1 downregulation and tight junction disruption via a TNF-α-regulated mechanism

AIM: To investigate the effect of bone-marrow mesenchymal stem cells (BM MSCs) on the intestinal mucosa barrier in ischemia/reperfusion (I/R) injury. METHODS: BM MSCs were isolated from male Sprague-Dawley rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. I/R injury was induced by occlusion of the superior mesenteric artery for 30 min. Rats were treated with saline, BM MSCs (via intramucosal injection) or tumor necrosis factor (TNF)-α blocking antibodies (via the tail vein). I/R injury was assessed using transmission electron microscopy, hematoxylin and eosin (HE) staining, immunohistochemistry, western blotting and enzyme linked immunosorbent assay.RESULTS: Intestinal permeability increased, tight junctions (TJs) were disrupted, and zona occludens 1 (ZO-1) was downregulated after I/R injury. BM MSCs reduced intestinal mucosal barrier destruction, ZO-1 downregulation, and TJ disruption. The morphological abnormalities after intestinal I/R injury positively correlated with serum TNF-α levels. Administration of anti-TNF-α IgG or anti-TNF-α receptor 1 antibodies attenuated the intestinal ultrastructural changes, ZO-1 downregulation, and TJ disruption. CONCLUSION: Altered serum TNF-α levels play an important role in the ability of BM MSCs to protect against intestinal I/R injury.

Role of mesenchymal stem cell derived extracellular vesicles in autoimmunity: A systematic review

BACKGROUND Mesenchymal stem cells(MSCs)have been reported to possess immune regulatory effects in innate and adaptive immune reactions.MSCs can mediate intercellular communications by releasing extracellular vesicles(EVs),which deliver functional molecules to targeted cells.MSC derived EVs(MSC-EVs)confer altering effects on many immune cells,including T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages.A large number of studies have suggested that MSC-EVs participate in regulating autoimmunity related diseases.This characteristic of MSC-EVs makes them be potential biomarkers for the diagnosis and treatment of autoimmunity related diseases.AIM To verify the potential of MSC-EVs for molecular targeted therapy of autoimmunity related diseases.METHODS Literature search was conducted in PubMed to retrieve the articles published between 2010 and 2020 in the English language.The keywords,such as“MSCs,”“EVs,”“exosome,”“autoimmunity,”“tumor immunity,”and“transplantation immunity,”and Boolean operator“AND”and“NOT”coalesced admirably to be used for searching studies on the specific molecular mechanisms of MSC-EVs in many immune cell types and many autoimmunity related diseases.Studies that did not investigate the molecular mechanisms of MSC-EVs in the occurrence and development of autoimmune diseases were excluded.RESULTS A total of 96 articles were chosen for final reference lists.After analyzing those publications,we found that it had been well documented that MSC-EVs have the ability to induce multiple immune cells,like T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages,to regulate immune responses in innate immunity and adaptive immunity.Many validated EVsdelivered molecules have been identified as key biomarkers,such as proteins,lipids,and nucleotides.Some EVs-encapsulated functional molecules can serve as promising therapeutic targets particularly for autoimmune disease.CONCLUSION MSC-EVs play an equally important part in the differentiation,activation,and proliferation of immune cells,and they may become potential biomarkers for diagnosis and treatment of autoimmunity related diseases.

Reflections on the New Classification of Tumors by the WHO and Changes in Esophageal Cancer in a High-risk Area

ABSTRACT In year 2000, a book entitled the Pathology and Genetics of Tumors of the Digestive System was published by the WHO, presenting some new diagnostic criteria and treatment principles. I have analyzed the epidemiologic change of tumors in over 30 years in the high-risk area with esophageal cancer. The following phenomenon was found： accompanied by the sharp decrease in the incidence and mortality of esophageal cancer, there was an increase in the incidence and death rate of stomach cancer involving cardiac cancer. This fact should be considered when analyzing the sharp decrease in esophageal cancer incidence and mortality rate. More attention was given to diagnosis of cardiac cancer; at the same time it is more practical to improve the early screening of cancers. To observe the development of high and low - grade intraepithelial neoplasms will be an urgent task for esophageal cancer research in the high risk area, according to WHO＇s new classification.

Mesenchymal Mandibular Chondrosarcoma: A Case Report and Review of Literature

Introduction: Chondrosarcomas (CS) are malignant cartilaginous tumors of rare maxillary localization. Their evolution is generally slow in time. They have a high tendency for locoregional recurrence after surgical treatment. Their prognosis depends on their degree of differentiation and the quality of resection. The authors report a clinical case of mesenchymal mandibular chondrosarcoma (MC), which is considered to be a subtype of CS, and specify the epidemiological, diagnostic, therapeutic and evolutionary features of this tumor. Case Report: A 73-year-old woman reported in February 2018 in our department complained of a slowly enlarging mass involving the right part of the lower jaw for the last 18 months. On examination a firm multilobular painful mass was palpated with cortical expansion, occupying the right side. A CT scan with 3D reconstruction was achieved and showed osteolysis lesions and cortical thickening. The mass biopsy for histological examination found a grade I well-differentiated bone chon-drosarcoma. We performed a hemi-mandibulectomy with complete resection of the tumor. The anatomopathologic examination of the resection specimen was in favour of a grade II mesenchymal chondrosarcoma. No radiotherapy was needed. The patient’s follow up was uneventful. Discussion: CS grading is the key to its management. Low grade CS (grades I and II) of the facial skeleton are luckily the most common, they are best treated with a local resection using 1.5 cm margins for bone and soft tissue. According to published literature, CS was historically considered as a radio resistant tumor. Radiotherapy and chemotherapy were therefore mainly reserved for high-grade tumors and for non-operable lesions. However, radical local surgery appears to be the treatment of choice for low grade chondrosarcoma. Conclusion: CS’s definitive diagnosis depends on appropriate radiographic evaluation along with adequate biopsy with meticulous histopathological examination and adjunctive immunohistochimical analysis. Neither chemotherapy nor radiotherapy is indicated as primary treatment. A long period follow-up should be advised as recurrence and metastasis are very frequent.

Mesenchymal stem cells promote the induction of colorectal cancer cells on normal intestinal epithelium

Objective:To establish a co-culture model of colon cancer cells or mesenchymal stem cells with normal colon epithelial cells in vitro for simulating the tumor microenvironment in vitro,and to investigate the effect of colon cancer cells or mesenchymal stem cells on the migration and epithelial-mesenchymal transformation(EMT)of normal colon epithelial cells in the co-culture environment.Method:Co-culture model of colon cancer cell line SW480 or human umbilical cord mesenchymal stem cells(hUC-MSCs)with human normal colon epithelial cells(NCM460)was established.Morphological changes of NCM460 after co-culture were evaluated by microscopic observation,and migration ability of NCM460 was measured by wound healing and Transwell assay.Meanwhile,Western blot was used to detect the EMT markers of NCM460.Results:There was no significant change in cell morphology of NCM460.Transwell assay results showed that when hUC-MSC or SW480 were co-cultured with NCM460,there is a trend of enhancement of the migration ability of NCM460,and the expression of Vimentin was up-regulated to some extent(P<0.05),E-cadherin and wound healing ability were not significantly changed(P>0.05).When NCM460 were cocultured with MSCs and SW480 at the same time,NCM460's wound healing ability and migration ability were significantly enhanced,meanwhile Vimentin protein expression was significantly up-regulated and E-cadherin protein was significantly down-regulated significantly(P<0.05).Conclusion:Colon cancer cells can increase the migration ability of normal colon epithelial cells and upregulate the expression of EMT markers.Mesenchymal stem cells may play a role in this process.

Autologous serum can induce mesenchymal stem cells into hepatocyte-like cells

Objective： To investigate whether the rabbit serum after radiofrequency ablation to liver tumor can induce mesenchymal stem cells （MSCs） differentiating into hepatocyte-like cells in order to find a new source and culture process for repairing liver injury. Methods： A tumor piece of 1 mm× 1mm×1 mm was transplanted into a tunnel at right liver of rabbits. The model of liver tumor was established after 2-3 weeks. The serum was collected from rabbits 72 h after being subjected to radiofrequency ablation of the liver tumor. Mesenchymal stem cells were isolated from rabbit bone marrow and cultured in DMEM containing autologous rabbit serum. Three kinds of media （L-DMEM） were tested respectively： ① containing 10% fetal calf serum （FCS）; ② containing 30% rabbit autologous serum after radiofrequency ablation of the liver tumor （ASRF）; ③ containing 30% rabbit autologous serum （AS）. MSCs were cultured on 12-well plates until passage 2 and examined under the light and electron microscopy at indicted intervals. The expression of albumin and CKl8 was detected using immunofluorescence to identify the characteristics of differentiated cells. Results： MSCs performed differently in the presence of fetal calf serum, rabbit autologous serum and rabbit autologous serum after radiofrequency ablation of the liver tumor. Induced by the serum after radiofrequency ablation to liver tumor for 7 d, the spindle-shaped MSCs turned into round shaped and resembled hepatocyte-like cells. The reactions were not found in MSCs cultured in FCS and AS groups. After induction for 14 d, slender microvilli, cell-cell junction structure and cholangiole emerged, and the differentiated cells expressed albumin and CKl 8. All those could not been observed in 10% FCS and 30% autologous serum groups. Conclusion： Mesenchymal stem cells differentiate into hepatocyte-like cells in the serum after radiofrequency ablation of liver tumor, providing us a potential cell source and culture process for clinical application in liver injury repairing.

Mesenchymal stem cells: A new diagnostic tool?

Mesenchymal stem cells(MSCs) are progenitor cells capable of self-renewal that can differentiate in multiple tissues and, under specific and standardizedculture conditions, expand in vitro with little phenotypic alterations. In recent years, preclinical and clinical studies have focused on MSC analysis and understanding the potential use of these cells as a therapy in a wide range of pathologies, and many applications have been tested. Clinical trials using MSCs have been performed(e.g., for cardiac events, stroke, multiple sclerosis, blood diseases, auto-immune disorders, ischemia, and articular cartilage and bone pathologies), and for many genetic diseases, these cells are considered an important resource. Considering of the biology of MSCs, these cells may also be useful tools for understanding the physiopathology of different diseases, and they can be used to develop specific biomarkers for a broad range of diseases. In this editorial, we discuss the literature related to the use of MSCs for diagnostic applications and we suggest new technologies to improve their employment.