BACKGROUND Kidney transplantation is associated with an increased risk of tumors in the urinary bladder.Among all the pathological types of tumors in the bladder,paraganglioma,which arises from extra-adrenal paragangl...BACKGROUND Kidney transplantation is associated with an increased risk of tumors in the urinary bladder.Among all the pathological types of tumors in the bladder,paraganglioma,which arises from extra-adrenal paraganglia and consists of chromaffin cells,is rare.Paragangliomas might cause severe clinical symptoms due to catecholamine hypersecretion or mass compression.Bladder paragangliomas are rare,especially those appearing after kidney transplantation.Here,we report a case of bladder paraganglioma developing after kidney transplantation.CASE SUMMARY A 63-year-old woman received a kidney transplant 12 years ago and took oral immunosuppressants(cyclosporine,mizoribine,and methylprednisolone)for regular post-transplant treatment.The patient felt no discomfort and she came to the hospital for a routine checkup.A mass located in the bladder was incidentally discovered by computed tomography,and she underwent surgical treatment.A 2 cm×2 cm invasive mass was found in the trigone of the bladder and the mass was removed.The diagnosis of paraganglioma was confirmed by morphology and immunophenotyping.The patient had a good prognosis and is still alive.CONCLUSION Paraganglioma can grow in the bladder,which might cause no clinical symptoms.The diagnosis mainly depends on morphology and immunophenotyping.Surgical resection is an important treatment option for such patients.展开更多
Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration...Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.展开更多
Purpose: To establish an animal model of autologous oral mucosa grafting for limbal stem cell deficiency.Methods: The study was carried from August to October2012. Fourteen SD rats were randomly and evenly allocated t...Purpose: To establish an animal model of autologous oral mucosa grafting for limbal stem cell deficiency.Methods: The study was carried from August to October2012. Fourteen SD rats were randomly and evenly allocated to study group A and control group B. Limbal stem cell deficiency was established by alkali burn in the right eye of each rat in both groups. Rats in group A received autologous oral mucosa strip transplantation following the chemical burn. Rats in group B did not receive surgery after the chemical burn.Topical antibiotics and dexamethasone were used in all rats.Corneal clarity, corneal fluorescein staining, oral mucosal graft survival, and complications at postoperative days 1,3,7,14 were observed.Results: The oral mucosa strip graft was detached in one rat in group A. Reepithelialization was observed starting from the graft position and was completed within 14 days in the remaining 6 eyes in group A. However, persistent corneal epithelium defect was observed in all eyes in group B, among which corneal melting and perforation was observed in 2 eyes and corneal opacification with neovascularization was observed in the remaining 5 eyes.Conclusion: Autologous oral mucosa strip grafting for limbal stem cell deficiency can be achieved by a rat model following chemical burn. The fate of the transplanted oral mucosal epithelial cells warrants further study.展开更多
BACKGROUND: Pancreas transplantation (PT) has proved effective but it is associated with a high risk of surgical complications and technical failure. Duct management and venous drainage are identified as major issues....BACKGROUND: Pancreas transplantation (PT) has proved effective but it is associated with a high risk of surgical complications and technical failure. Duct management and venous drainage are identified as major issues. Improvements in immunosuppression and prophylaxis greatly have contributed to surgical progress. DATA SOURCES: A literature search of the PubMed database (1996-2005) was conducted and research articles on PT reviewed. RESULTS: More than 23 000 PTs have been performed throughout the world. The majority (83%) were performed in combination with kidney transplantation [simultaneous pancreas-kidney transplantation (SPK)]. Pancreas graft survival rates at one year were 85% for 2001-2003 SPK cases, 79% for pancreas after kidney transplantation (PAK) cases, and 76% for pancreas transplantation alone (PTA) cases. For the 1999-2003 cases, enteric drainage was done in 79% of the SPK cases and bladder drainage in 21%. Patient survival rates, pancreas and kidney graft survival rates, and pancreas graft immunological failure rates did not differ significantly in enteric versus bladder drainage cases. All the available data fail to demonstrate a definitive advantage of portal drainage over systemic drainage. From 1993 to 2002, the use of rabbit antithymocyte globulin increased from 0 to 37%; the use of daclizumab increased from 0 to 16%; and the use of basiliximab increased from 0 to 25%. In 1993, 98% of SPK recipients received cyclosporine; but this was decreased to 9% in 2002. Tacrolimus (FK506) usage has increased from 0 (1993) to 87% (2002) of SPK recipients. Sirolimus (SIR) usage has increased from 0 (1993) to 18% (2002) of SPK recipients. CONCLUSIONS: PT remains an effective therapy for treatment of type I diabetes mellitus. Enteric drainage is currently predominant in SPK, but bladder drainage is still largely used. Portal drainage is as safe as systemic drainage, but there is still no convincing evidence about whether it is immunologically or metabolically convenient. The combined of FK506 and mycophenolate mophetil (MMF) is the preferred maintenance immunosuppression in PT. Sirolimus may be a good alternative as a second agent in recipients of PT under FK506 therapy.展开更多
AIM: To explore the protective effect of bone marrow mesenchymal stem cells (BM MSCs) in the small intestinal mucosal barrier following heterotopic intestinal transplantation (HIT) in a rat model.
BACKGROUND Pelvic lipomatosis is a rare disease of unknown etiology,characterized by the overgrowth of pelvic adipose tissue that causes compression of the urinary tract including the bladder and ureters,rectum and bl...BACKGROUND Pelvic lipomatosis is a rare disease of unknown etiology,characterized by the overgrowth of pelvic adipose tissue that causes compression of the urinary tract including the bladder and ureters,rectum and blood vessels.The patient may progressively develop obstructive uropathy which could subsequently lead to renal failure.At present,there are no reports of renal transplantation due to uremia caused by pelvic lipomatosis.The ideal management of patients with pelvic lipomatosis after renal transplantation is not yet well-established due to the lack of literature and follow-up data.CASE SUMMARY We report a 37-year-old male patient with pelvic lipomatosis who received a successful living donor renal transplantation on July 22,2015.The operation was complicated as the iliac vessels and bladder were wrapped entirely in excessive abnormal fat.The external iliac artery and vein were located using ultrasonographic guidance.The adipose tissue around the right bladder was removed as far as possible,and the graft ureter was reimplanted into the bladder,using the Lich-Gregoir technique.At 22 mo after transplantation,graft percutaneous nephrostomy was performed under ultrasonographic guidance for urinary diversion due to hydronephrosis of the graft kidney.Follow-up at four years showed that the renal allograft function was stable.CONCLUSION When patients with pelvic lipomatosis develop renal failure,renal transplantation could be a feasible treatment strategy.展开更多
The history of vascularized pancreas transplantation largely parallels developments in immunosuppression and technical refinements in transplant surgery. From the late-1980 s to 1995, most pancreas transplants were wh...The history of vascularized pancreas transplantation largely parallels developments in immunosuppression and technical refinements in transplant surgery. From the late-1980 s to 1995, most pancreas transplants were whole organ pancreatic grafts with insulin delivery to the iliac vein and diversion of the pancreatic ductal secretions to the urinary bladder(systemic-bladder technique). The advent of bladder drainage revolutionized the safety and improved the success of pancreas transplantation. However, starting in 1995, a seismic change occurred from bladder to bowel exocrine drainage coincident with improvements in immunosuppression, preservation techniques, diagnostic monitoring, general medical care, and the success and frequency of enteric conversion. In the new millennium, pancreas transplants are performed predominantly as pancreatico-duodenal grafts with enteric diversion of the pancreatic ductal secretions coupled with iliac vein provision of insulin(systemic-enteric technique) although the systemic-bladder technique endures as a preferred alternative in selected cases. In the early 1990 s, a novel technique of venous drainage into the superior mesenteric vein combined with bowel exocrine diversion(portal-enteric technique) was designed and subsequently refined over the next ≥ 20 years to recreate the natural physiology of the pancreas with firstpass hepatic processing of insulin. Enteric drainage usually refers to jejunal or ileal diversion of the exocrine secretions either with a primary enteric anastomosis or with an additional Roux limb. The portal-enteric technique has spawned a number of newer and revisited techniques of enteric exocrine drainage including duodenal or gastric diversion. Reports in the literature suggest no differences in pancreas transplant outcomes irrespective of type of either venous or exocrine diversion. The purpose of this review is to examine theliterature on exocrine drainage in the new millennium(the purported "enteric drainage" era) with special attention to technical variations and nuances in vascularized pancreas transplantation that have been proposed and studied in this time period.展开更多
The patient-derived xenografts (PDX) model is an animal model established by transplanting primary tumors or fresh tumor tissues of patient origin directly into immunodeficient mice, which preserves the heterogeneity ...The patient-derived xenografts (PDX) model is an animal model established by transplanting primary tumors or fresh tumor tissues of patient origin directly into immunodeficient mice, which preserves the heterogeneity and survival microenvironment of the primary tumor and is widely used in preclinical and precision medicine research of tumors. This article reviews the construction of the PDX model of human bladder cancer and the progress of the application of the PDX model in bladder cancer.展开更多
Neurogenic bladder ( NB) dysfunction caused by spinal cord injury ( SCI ) or diseases of the central nervous system or peripheral nerves is a major medical and social problem. Traditional treatments to NB include ...Neurogenic bladder ( NB) dysfunction caused by spinal cord injury ( SCI ) or diseases of the central nervous system or peripheral nerves is a major medical and social problem. Traditional treatments to NB include medication, injection of Botulinum toxin A into the detrusor, neuromodulation and surgery. There are also emerging approaches, such as tissue engineering, stem cell transplantation and gene therapy. In recent years, we have carried out explorations in both therapeutic areas and tried to translate basic research into clinical practice. This paper reviews our work in this regard, and provides references for future research.展开更多
To evaluate the operative characteristics and efficacy of retroperitoneoscopic resection of renal,ureter and partial bladder for the treatment of native renal pelvic and ureteral transitional cell cancer occurring at ...To evaluate the operative characteristics and efficacy of retroperitoneoscopic resection of renal,ureter and partial bladder for the treatment of native renal pelvic and ureteral transitional cell cancer occurring at the same side of transplanted kidney.Methods In 5 cases of renal transplantation,there were 2 cases of right native renal pelvic cancer,1 case of right native renal pelvic and ureter cancer and 2 cases of right ureter cancer respectively.The transplanted kidney was in the same iliac fossa side of the tumor.All 5 patients were subjected to nephroureterectomy and bladder cuff excision by retroperitoneoscopic technique.Results Five operations were completed successfully.The operative time was 180 to 280 min,and the blood loss was 50 to 200 ml.The recovery of intestinal function after operation was 12 to 36 h.The urine output was 1 500 to 4 000 per day.Postoperative serum creatinine was still normal.The mean hospital stay after operation was 4.5 days.Conclusion Retroperitoneal laparoscopic nephroureterectomy and bladder cuff excision is a good method to treat the native renal pelvic and ureteral transitional cell cancer occurring at the same side of transplanted kidney.The procedure is safe and less invasive,which provides a good protection of transplanted kidney.12 refs.展开更多
Primary sclerosing cholangitis(PSC)is an immune-related chronic cholangiopathy associated with high rates of progression to liver cirrhosis and the need for liver transplantation.Since PSC is frequently associated wit...Primary sclerosing cholangitis(PSC)is an immune-related chronic cholangiopathy associated with high rates of progression to liver cirrhosis and the need for liver transplantation.Since PSC is frequently associated with inflammatory bowel disease(IBD),several studies have investigated the role of the gut-liver axis in PSC and emerging evidence indicates that gut and bile microbiota are associated with the onset and progression of PSC[reviewed in(1)].展开更多
The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabofism. The influence of th...The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabofism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBT and the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allografl rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host-microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.展开更多
Background and Objective:Limbal stem cell deficiency(LSCD)is characterized by the insufficiency of limbal stem cells to maintain the corneal epithelium.Severe cases of LSCD may be treated with limbal transplantation f...Background and Objective:Limbal stem cell deficiency(LSCD)is characterized by the insufficiency of limbal stem cells to maintain the corneal epithelium.Severe cases of LSCD may be treated with limbal transplantation from healthy autologous or allogeneic limbal tissue.Multiple cell-based therapies have been studied as alternative treatments to improve success rates and minimize immunosuppressive regimens after allogeneic transplants.In this review,we describe the success rates,and complications of different cell-based therapies for LSCD.We also discuss each therapy’s relative strengths and weaknesses,their history in animal and human studies,and their effectiveness compared to traditional transplants.Methods:PubMed was searched for publications using the terms LSCD,cell-based therapy,cultivated limbal epithelial transplantation(CLET),cultivated oral mucosal epithelial transplantation(COMET),and mesenchymal stem cells from 1989 to August 2022.Inclusion criteria were English language articles.Exclusion criteria were non-English language articles.Key Content and Findings:current cell-based therapies for LSCD are CLET and non-limbal epithelial cells.Non-limbal epithelial cell methods include COMET,conjunctival epithelial autografts,and mesenchymal stem/stromal cells(MSCs).Moreover,several alternative potential sources of non-limbal cells have described,including induced pluripotent stem cells(iPSCs),human embryonic stem cells(hESCs),human dental pulp stem cells,hair follicle bulge-derived epithelial stem cells,amniotic membrane epithelial cells,and human umbilical cord lining epithelial cells.Conclusions:Cell-based therapies are a promising treatment modality for LSCD.While CLET is currently the only approved cell-based therapy and is only approved in the European Union,more novel methods have also been shown to be effective in human or animal studies thus far.Non-limbal epithelial cells such as COMET are also an alternative treatment to allogeneic transplants especially as a surface stabilizing procedure.iPSCs are currently being studied in early phase trials and have the potential to revolutionize the way LSCD is treated.Lastly,cell-based therapies for restoring the limbal niche such as mesenchymal stem cells have also shown promising results in the first human proof-of-concept study.Several potential sources of non-limbal cells are under investigation.展开更多
文摘BACKGROUND Kidney transplantation is associated with an increased risk of tumors in the urinary bladder.Among all the pathological types of tumors in the bladder,paraganglioma,which arises from extra-adrenal paraganglia and consists of chromaffin cells,is rare.Paragangliomas might cause severe clinical symptoms due to catecholamine hypersecretion or mass compression.Bladder paragangliomas are rare,especially those appearing after kidney transplantation.Here,we report a case of bladder paraganglioma developing after kidney transplantation.CASE SUMMARY A 63-year-old woman received a kidney transplant 12 years ago and took oral immunosuppressants(cyclosporine,mizoribine,and methylprednisolone)for regular post-transplant treatment.The patient felt no discomfort and she came to the hospital for a routine checkup.A mass located in the bladder was incidentally discovered by computed tomography,and she underwent surgical treatment.A 2 cm×2 cm invasive mass was found in the trigone of the bladder and the mass was removed.The diagnosis of paraganglioma was confirmed by morphology and immunophenotyping.The patient had a good prognosis and is still alive.CONCLUSION Paraganglioma can grow in the bladder,which might cause no clinical symptoms.The diagnosis mainly depends on morphology and immunophenotyping.Surgical resection is an important treatment option for such patients.
基金supported in part by NIH R01 NS100531,R01 NS103481NIH R21NS130241(to LD)+3 种基金Merit Review Award I01 BX002356,I01 BX003705 from the U.S.Department of Veterans AffairsIndiana Spinal Cord and Brain Injury Research Foundation(No.19919)Mari Hulman George Endowment Funds(to XMX)Indiana Spinal Cord&Brain Injury Research Fund from ISDH(to NKL and LD)。
文摘Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.
基金Young Teachers Cultivation Project of Sun Yat-sen University(10ykpy25)Doctoral Program of the Ministry of Education(20110171120104)Science and Technology Programs of Guangdong Province(2010B060200008,201213031800456)
文摘Purpose: To establish an animal model of autologous oral mucosa grafting for limbal stem cell deficiency.Methods: The study was carried from August to October2012. Fourteen SD rats were randomly and evenly allocated to study group A and control group B. Limbal stem cell deficiency was established by alkali burn in the right eye of each rat in both groups. Rats in group A received autologous oral mucosa strip transplantation following the chemical burn. Rats in group B did not receive surgery after the chemical burn.Topical antibiotics and dexamethasone were used in all rats.Corneal clarity, corneal fluorescein staining, oral mucosal graft survival, and complications at postoperative days 1,3,7,14 were observed.Results: The oral mucosa strip graft was detached in one rat in group A. Reepithelialization was observed starting from the graft position and was completed within 14 days in the remaining 6 eyes in group A. However, persistent corneal epithelium defect was observed in all eyes in group B, among which corneal melting and perforation was observed in 2 eyes and corneal opacification with neovascularization was observed in the remaining 5 eyes.Conclusion: Autologous oral mucosa strip grafting for limbal stem cell deficiency can be achieved by a rat model following chemical burn. The fate of the transplanted oral mucosal epithelial cells warrants further study.
文摘BACKGROUND: Pancreas transplantation (PT) has proved effective but it is associated with a high risk of surgical complications and technical failure. Duct management and venous drainage are identified as major issues. Improvements in immunosuppression and prophylaxis greatly have contributed to surgical progress. DATA SOURCES: A literature search of the PubMed database (1996-2005) was conducted and research articles on PT reviewed. RESULTS: More than 23 000 PTs have been performed throughout the world. The majority (83%) were performed in combination with kidney transplantation [simultaneous pancreas-kidney transplantation (SPK)]. Pancreas graft survival rates at one year were 85% for 2001-2003 SPK cases, 79% for pancreas after kidney transplantation (PAK) cases, and 76% for pancreas transplantation alone (PTA) cases. For the 1999-2003 cases, enteric drainage was done in 79% of the SPK cases and bladder drainage in 21%. Patient survival rates, pancreas and kidney graft survival rates, and pancreas graft immunological failure rates did not differ significantly in enteric versus bladder drainage cases. All the available data fail to demonstrate a definitive advantage of portal drainage over systemic drainage. From 1993 to 2002, the use of rabbit antithymocyte globulin increased from 0 to 37%; the use of daclizumab increased from 0 to 16%; and the use of basiliximab increased from 0 to 25%. In 1993, 98% of SPK recipients received cyclosporine; but this was decreased to 9% in 2002. Tacrolimus (FK506) usage has increased from 0 (1993) to 87% (2002) of SPK recipients. Sirolimus (SIR) usage has increased from 0 (1993) to 18% (2002) of SPK recipients. CONCLUSIONS: PT remains an effective therapy for treatment of type I diabetes mellitus. Enteric drainage is currently predominant in SPK, but bladder drainage is still largely used. Portal drainage is as safe as systemic drainage, but there is still no convincing evidence about whether it is immunologically or metabolically convenient. The combined of FK506 and mycophenolate mophetil (MMF) is the preferred maintenance immunosuppression in PT. Sirolimus may be a good alternative as a second agent in recipients of PT under FK506 therapy.
基金Supported by The Natural Science Foundation of China,No.81270528the Natural Science Foundation of Tianjin,China,No.08JCYBJC08400,No.11JCZDJC27800 and No.12JCZDJC25200the Technology Foundation of Health Bureau of Tianjin,China,No.2011KY11
文摘AIM: To explore the protective effect of bone marrow mesenchymal stem cells (BM MSCs) in the small intestinal mucosal barrier following heterotopic intestinal transplantation (HIT) in a rat model.
基金Supported by National Natural Science Foundation of China,No.81970654。
文摘BACKGROUND Pelvic lipomatosis is a rare disease of unknown etiology,characterized by the overgrowth of pelvic adipose tissue that causes compression of the urinary tract including the bladder and ureters,rectum and blood vessels.The patient may progressively develop obstructive uropathy which could subsequently lead to renal failure.At present,there are no reports of renal transplantation due to uremia caused by pelvic lipomatosis.The ideal management of patients with pelvic lipomatosis after renal transplantation is not yet well-established due to the lack of literature and follow-up data.CASE SUMMARY We report a 37-year-old male patient with pelvic lipomatosis who received a successful living donor renal transplantation on July 22,2015.The operation was complicated as the iliac vessels and bladder were wrapped entirely in excessive abnormal fat.The external iliac artery and vein were located using ultrasonographic guidance.The adipose tissue around the right bladder was removed as far as possible,and the graft ureter was reimplanted into the bladder,using the Lich-Gregoir technique.At 22 mo after transplantation,graft percutaneous nephrostomy was performed under ultrasonographic guidance for urinary diversion due to hydronephrosis of the graft kidney.Follow-up at four years showed that the renal allograft function was stable.CONCLUSION When patients with pelvic lipomatosis develop renal failure,renal transplantation could be a feasible treatment strategy.
文摘The history of vascularized pancreas transplantation largely parallels developments in immunosuppression and technical refinements in transplant surgery. From the late-1980 s to 1995, most pancreas transplants were whole organ pancreatic grafts with insulin delivery to the iliac vein and diversion of the pancreatic ductal secretions to the urinary bladder(systemic-bladder technique). The advent of bladder drainage revolutionized the safety and improved the success of pancreas transplantation. However, starting in 1995, a seismic change occurred from bladder to bowel exocrine drainage coincident with improvements in immunosuppression, preservation techniques, diagnostic monitoring, general medical care, and the success and frequency of enteric conversion. In the new millennium, pancreas transplants are performed predominantly as pancreatico-duodenal grafts with enteric diversion of the pancreatic ductal secretions coupled with iliac vein provision of insulin(systemic-enteric technique) although the systemic-bladder technique endures as a preferred alternative in selected cases. In the early 1990 s, a novel technique of venous drainage into the superior mesenteric vein combined with bowel exocrine diversion(portal-enteric technique) was designed and subsequently refined over the next ≥ 20 years to recreate the natural physiology of the pancreas with firstpass hepatic processing of insulin. Enteric drainage usually refers to jejunal or ileal diversion of the exocrine secretions either with a primary enteric anastomosis or with an additional Roux limb. The portal-enteric technique has spawned a number of newer and revisited techniques of enteric exocrine drainage including duodenal or gastric diversion. Reports in the literature suggest no differences in pancreas transplant outcomes irrespective of type of either venous or exocrine diversion. The purpose of this review is to examine theliterature on exocrine drainage in the new millennium(the purported "enteric drainage" era) with special attention to technical variations and nuances in vascularized pancreas transplantation that have been proposed and studied in this time period.
文摘The patient-derived xenografts (PDX) model is an animal model established by transplanting primary tumors or fresh tumor tissues of patient origin directly into immunodeficient mice, which preserves the heterogeneity and survival microenvironment of the primary tumor and is widely used in preclinical and precision medicine research of tumors. This article reviews the construction of the PDX model of human bladder cancer and the progress of the application of the PDX model in bladder cancer.
文摘Neurogenic bladder ( NB) dysfunction caused by spinal cord injury ( SCI ) or diseases of the central nervous system or peripheral nerves is a major medical and social problem. Traditional treatments to NB include medication, injection of Botulinum toxin A into the detrusor, neuromodulation and surgery. There are also emerging approaches, such as tissue engineering, stem cell transplantation and gene therapy. In recent years, we have carried out explorations in both therapeutic areas and tried to translate basic research into clinical practice. This paper reviews our work in this regard, and provides references for future research.
文摘To evaluate the operative characteristics and efficacy of retroperitoneoscopic resection of renal,ureter and partial bladder for the treatment of native renal pelvic and ureteral transitional cell cancer occurring at the same side of transplanted kidney.Methods In 5 cases of renal transplantation,there were 2 cases of right native renal pelvic cancer,1 case of right native renal pelvic and ureter cancer and 2 cases of right ureter cancer respectively.The transplanted kidney was in the same iliac fossa side of the tumor.All 5 patients were subjected to nephroureterectomy and bladder cuff excision by retroperitoneoscopic technique.Results Five operations were completed successfully.The operative time was 180 to 280 min,and the blood loss was 50 to 200 ml.The recovery of intestinal function after operation was 12 to 36 h.The urine output was 1 500 to 4 000 per day.Postoperative serum creatinine was still normal.The mean hospital stay after operation was 4.5 days.Conclusion Retroperitoneal laparoscopic nephroureterectomy and bladder cuff excision is a good method to treat the native renal pelvic and ureteral transitional cell cancer occurring at the same side of transplanted kidney.The procedure is safe and less invasive,which provides a good protection of transplanted kidney.12 refs.
基金Funding:DFG Emmy Noether Program to MS(SI 19834/1)ERC Starting Grant REVERT to MS,BMBF PACE Therapy Grant to MSEinstein Foundation EC3R to MS.
文摘Primary sclerosing cholangitis(PSC)is an immune-related chronic cholangiopathy associated with high rates of progression to liver cirrhosis and the need for liver transplantation.Since PSC is frequently associated with inflammatory bowel disease(IBD),several studies have investigated the role of the gut-liver axis in PSC and emerging evidence indicates that gut and bile microbiota are associated with the onset and progression of PSC[reviewed in(1)].
文摘The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabofism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBT and the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allografl rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host-microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.
基金supported by the National Eye Institute/National Institutes of Health and the Core Grant for Vision Research[R01 EY024349(ARD),UH3 EY031809(ARD),EY01792]Department of Defense Vision Research Program–Congressionally Directed Medical Research Program[VR170180]Research to Prevent Blindness Unrestricted Grant to the department and Physician-Scientist Award.
文摘Background and Objective:Limbal stem cell deficiency(LSCD)is characterized by the insufficiency of limbal stem cells to maintain the corneal epithelium.Severe cases of LSCD may be treated with limbal transplantation from healthy autologous or allogeneic limbal tissue.Multiple cell-based therapies have been studied as alternative treatments to improve success rates and minimize immunosuppressive regimens after allogeneic transplants.In this review,we describe the success rates,and complications of different cell-based therapies for LSCD.We also discuss each therapy’s relative strengths and weaknesses,their history in animal and human studies,and their effectiveness compared to traditional transplants.Methods:PubMed was searched for publications using the terms LSCD,cell-based therapy,cultivated limbal epithelial transplantation(CLET),cultivated oral mucosal epithelial transplantation(COMET),and mesenchymal stem cells from 1989 to August 2022.Inclusion criteria were English language articles.Exclusion criteria were non-English language articles.Key Content and Findings:current cell-based therapies for LSCD are CLET and non-limbal epithelial cells.Non-limbal epithelial cell methods include COMET,conjunctival epithelial autografts,and mesenchymal stem/stromal cells(MSCs).Moreover,several alternative potential sources of non-limbal cells have described,including induced pluripotent stem cells(iPSCs),human embryonic stem cells(hESCs),human dental pulp stem cells,hair follicle bulge-derived epithelial stem cells,amniotic membrane epithelial cells,and human umbilical cord lining epithelial cells.Conclusions:Cell-based therapies are a promising treatment modality for LSCD.While CLET is currently the only approved cell-based therapy and is only approved in the European Union,more novel methods have also been shown to be effective in human or animal studies thus far.Non-limbal epithelial cells such as COMET are also an alternative treatment to allogeneic transplants especially as a surface stabilizing procedure.iPSCs are currently being studied in early phase trials and have the potential to revolutionize the way LSCD is treated.Lastly,cell-based therapies for restoring the limbal niche such as mesenchymal stem cells have also shown promising results in the first human proof-of-concept study.Several potential sources of non-limbal cells are under investigation.