RESUMO
INTRODUCTION: Perihilar cholangiocarcinoma is a difficult cancer to treat with frequent vascular invasion, local recurrence, and poor survival. Due to the need for biliary anastomosis and potential vascular resection, the standard approach is an open operation. Suboptimal outcomes after laparoscopic resection had been sporadically reported by high-volume centers. In this first, Trans-Atlantic, multicenter study, we report our outcomes of robotic resection for perihilar cholangiocarcinoma. This is the largest study of its kind in the Western hemisphere. METHODS: Between 2016 and 2023, we prospectively followed patients undergoing robotic resection for perihilar cholangiocarcinoma at three, high-volume, robotic, liver-surgery centers. RESULTS: Thirty-eight patients underwent perihilar cholangiocarcinoma utilizing the robotic technique; Klatskin type-3 was the most common. The median age was 72 years, and 82% of the patients underwent preoperative biliary drainage. Median operative time was 481 minutes with a median estimated blood loss of 200 mL. The number of harvested lymph nodes was seven, and 11 (28%) patients yielded positive lymph nodes. Three patients required vascular reconstruction; 18% of patients had >1 biliary anastomosis. R0 resection margins were achieved in 82% of patients. Clavien-Dindo Grade ≥3 complications were seen in 16% of patients. The length of stay was 6 days. Five patients had an unplanned readmission within 30 days. One patient died within 30 days. With a median follow-up of 15 months, 68% of patients are alive without disease, 13% recurred, and 19% died. CONCLUSIONS: Application of the robotic platform for perihilar cholangiocarcinoma is safe and feasible with acceptable short-term clinical and oncological outcomes.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Idoso , Tumor de Klatskin/patologia , Procedimentos Cirúrgicos Robóticos/métodos , Hepatectomia/métodos , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/cirurgia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVES: We aimed to describe our outcomes of robotic resection for perihilar cholangiocarcinoma, the largest single institutional series in the Western hemisphere to date. METHODS: Between 2016 and 2022, we prospectively followed all patients who underwent robotic resection for perihilar cholangiocarcinoma. RESULTS: In total, 23 patients underwent robotic resection for perihilar cholangiocarcinoma, 18 receiving concomitant hepatectomy. The median age was 73 years. Operative time was 470 min with an estimated blood loss of 150 mL. No intraoperative conversions to open or other intraoperative complications occurred. Median length of stay was 5 days. Four postoperative complications occurred. Three readmissions occurred within 30 days with one 90-day mortality. R0 resection was achieved in 87% of patients and R1 in 13% of patients. At a median follow-up of 27 months, 15 patients were alive without evidence of disease, two patients with local recurrence at 1 year, and six were deceased. CONCLUSIONS: Utilization of the robotic platform for perihilar cholangiocarcinoma is safe and feasible with excellent perioperative outcomes. Further studies are needed to determine the long-term oncological outcomes.
Assuntos
Neoplasias dos Ductos Biliares , Hepatectomia , Tumor de Klatskin , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/mortalidade , Masculino , Feminino , Idoso , Tumor de Klatskin/cirurgia , Tumor de Klatskin/patologia , Tumor de Klatskin/mortalidade , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/mortalidade , Pessoa de Meia-Idade , Estudos Prospectivos , Hepatectomia/métodos , Hepatectomia/mortalidade , Idoso de 80 Anos ou mais , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Seguimentos , Resultado do Tratamento , Tempo de Internação/estatística & dados numéricos , Duração da CirurgiaRESUMO
INTRODUCTION: Most of the literature has only reported outcomes on robotic minor non-anatomical hepatectomy. This study was undertaken to analyze and examine the safety, feasibly, and perioperative outcomes of robotic major hepatectomy at our institution. METHODS: All patients undergoing robotic major hepatectomy were prospectively followed. Major hepatectomy was defined as a resection of 3 or more segments. Data are expressed as median (mean ± SD). RESULTS: A total of 170 consecutive patients underwent robotic hepatectomies, of which 100 were major resections involving at least 3 segments. The 100 patients were of median 62 (61 ± 13.0) years, and 46% were women. Median BMI was 29 (29 ± 5.9) kg/m2 and median ASA class was 3 (3 ± 0.5). Thirty percent of robotic major hepatectomies were for hepatocellular carcinoma, 28% were for metastatic adenocarcinoma, 9% were for cholangiocarcinoma, and 5% were for metastatic neuroendocrine tumor. Prep time (in the room until incision) was a median 58 min (62 ± 18.4), extraction time (incision until specimen extraction) was 124 min (146 ± 99.5), console time was 198 min (210 ± 123.9), closure time (extraction until dressing placement) was 109 min (131 ± 93.8), operative duration was 246 min (269 ± 123.2), and time under anesthesia was 330 min (353 ± 109.6). Estimated blood loss was 175 ml (249 ± 275.9) and length of stay was 4 days (5 ± 4.3). Seven patients experienced postoperative complications. Thirteen patients were readmitted within 30 days, and one patient died within 30 days. CONCLUSION: Application of the robotic platform to major hepatectomy is safe and feasible. Our early experience shows that this minimally invasive approach results in excellent short-term outcomes.
Assuntos
Laparoscopia , Neoplasias Hepáticas , Procedimentos Cirúrgicos Robóticos , Idoso , Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Feminino , Hepatectomia , Humanos , Tempo de Internação , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias , Estudos RetrospectivosRESUMO
Research of the opioid system and its composite receptors and ligands has revealed its promise as a potential therapy for neurodegenerative diseases such as stroke and Parkinson's Disease. In particular, delta opioid receptors (DORs) have been elucidated as a therapeutically distinguished subset of opioid receptors and a compelling target for novel intervention techniques. Research is progressively shedding light on the underlying mechanism of DORs and has revealed two mechanisms of DOR neuroprotection; DORs function to maintain ionic homeostasis and also to trigger endogenous neuroprotective pathways. Delta opioid agonists such as (D-Ala2, D-Leu5) enkephalin (DADLE) have been shown to promote neuronal survival and decrease apoptosis, resulting in a substantial amount of research for its application as a neurological therapeutic. Most notably, DADLE has demonstrated significant potential to reduce cell death following ischemic events. Current research is working to reveal the complex mechanisms of DADLE's neuroprotective properties. Ultimately, our knowledge of the DOR receptors and agonists has made the opioid system a promising target for therapeutic intervention in many neurological disorders.
Assuntos
Leucina Encefalina-2-Alanina/farmacologia , Doenças do Sistema Nervoso/tratamento farmacológico , Peptídeos Opioides/farmacologia , Receptores Opioides delta/efeitos dos fármacos , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Leucina Encefalina-2-Alanina/uso terapêutico , Humanos , Doenças do Sistema Nervoso/fisiopatologia , Peptídeos Opioides/uso terapêutico , Acidente Vascular Cerebral/fisiopatologiaRESUMO
Stem cells exhibit simple and naive cellular features, yet their exact purpose for regenerative medicine continues to elude even the most elegantly designed research paradigms from developmental biology to clinical therapeutics. Based on their capacity to divide indefinitely and their dynamic differentiation into any type of tissue, the advent of transplantable stem cells has offered a potential treatment for aging-related and injury-mediated diseases. Recent laboratory evidence has demonstrated that transplanted human neural stem cells facilitate endogenous reparative mechanisms by initiating multiple regenerative processes in the brain neurogenic areas. Within these highly proliferative niches reside a myriad of potent regenerative molecules, including anti-inflammatory cytokines, proteomes, and neurotrophic factors, altogether representing a biochemical cocktail vital for restoring brain function in the aging and diseased brain. Here, we advance the concept of therapeutically repurposing stem cells not towards cell replacement per se, but rather exploiting the cells' intrinsic properties to serve as the host brain regenerative catalysts.
Assuntos
Células-Tronco Neurais/citologia , Neurogênese , Medicina Regenerativa , Transplante de Células-Tronco , Diferenciação Celular , Humanos , Nicho de Células-TroncoRESUMO
Accumulating evidence has demonstrated that menstrual blood stands as a viable source of stem cells. Menstrual blood-derived stem cells (MenSCs) are morphologically and functionally similar to cells directly extracted from the endometrium, and present dual expression of mesenchymal and embryonic cell markers, thus becoming interesting tools for regenerative medicine. Functional reports show higher proliferative and self-renewal capacities than bone marrow-derived stem cells, as well as successful differentiation into hepatocyte-like cells, glial-like cells, endometrial stroma-like cells, among others. Moreover, menstrual blood stem cells may be used with increased efficiency in reprogramming techniques for induced Pluripotent Stem cell (iPS) generation. Experimental studies have shown successful treatment of stroke, colitis, limb ischemia, coronary disease, Duchenne's muscular atrophy and streptozotocin-induced type 1 diabetes animal models with MenSCs. As we envision an off-the-shelf product for cell therapy, cryopreserved MenSCs appear as a feasible clinical product. Clinical applications, although still very limited, have great potential and ongoing studies should be disclosed in the near future.
Assuntos
Colite/terapia , Criopreservação/métodos , Endométrio/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Distrofia Muscular de Duchenne/terapia , Acidente Vascular Cerebral/terapia , Animais , Diferenciação Celular , Proliferação de Células , Separação Celular/métodos , Ensaios Clínicos como Assunto , Colite/patologia , Criopreservação/ética , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/terapia , Modelos Animais de Doenças , Endométrio/fisiologia , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologia , Menstruação/fisiologia , Camundongos , Distrofia Muscular de Duchenne/patologia , Acidente Vascular Cerebral/patologiaRESUMO
ABSTRACT: Evidence-based decision-making is generally based on published evidence. Therefore, if the published evidence is biased, so will the decision-making. One possible bias is the "positive-results" publication bias. This study attempts to characterize this phenomenon in cataract therapy trials. Studies were categorized as "positive" if their results were congruent with the hypothesis and "negative" if not. Secondary outcomes included the influence of funding source and differences in publication metrics between "positive" and "negative" publications. The US NLM Clinical Trials database was reviewed for cataract trials, yielding 248 trials. Trials with less than 2 treatment arms, less than 5 participants, or insufficient reporting were excluded. Data was collected on intervention, treatment arms, funding type, publication rates, citation rate, and the impact factor/H-index of journals. Of the 132 trials included, there were 69 positive and 63 negative results. Publication rate for positive results (71%) was significantly greater than negative results (17%), (p<0.01), with no significant difference in the other publication metrics. In conclusion, "negative" result trials are published less frequently, but are equally valued, if published. There are implications for evidence-based medicine with these findings.
RESUMO
PURPOSE: Evidence-based medicine requires evaluation of the medical literature to guide clinical reasoning and treatment recommendations. The presence of publication bias towards exclusion of non-statistically significant clinical trials may be leading to an incomplete evaluation of the literature and cause potentially incomplete guidance for patients. We aimed to compare publication rates and impact of publications of positive and negative outcome clinical trials. METHODS: We queried the US National Library of Medicine Clinical Trials database identifying clinical trials with reported results on the topics of pancreatic, liver, and gastric cancer. A "positive" trial was defined as having a statistically significant difference between the treatment arms, while a "negative" did not. Data collected included termination cause, intervention, funding type, publication rates, and journal characteristics. RESULTS: In total, 535 clinical trials were examined, across all pathologies clinical trials with significant findings for the primary outcome were published at a higher rate (99%) compared to those with non-significant findings (77%) (p < 0.01). Significantly, more studies with significant findings reached at least 80% of their estimated enrollment goal versus non-significant studies, 72% and 53% respectively (p < 0.01). Three of four metrics for impact of publication showed no difference between significant and non-significant studies once they reached publication. CONCLUSION: These findings suggest that clinical trials of three of the most common upper gastrointestinal malignancies have a publication bias towards studies with significant primary outcome findings. This study has implications to the way evidence-based medicine is practiced as the medical literature appears to be failing to capture important data for consideration of clinical decision making.
Assuntos
Ensaios Clínicos como Assunto , Viés de Publicação , Humanos , Ensaios Clínicos como Assunto/estatística & dados numéricos , Neoplasias Gastrointestinais/terapia , Neoplasias Gastrointestinais/patologia , Medicina Baseada em Evidências/normas , Medicina Baseada em Evidências/estatística & dados numéricos , Medicina Baseada em Evidências/métodos , Neoplasias Hepáticas/terapia , Neoplasias Gástricas/terapia , Neoplasias Pancreáticas/terapiaRESUMO
Studies regarding the influence of diabetes on perioperative outcomes after major hepatectomy are conflicting. The objective of this study is to analyze the effects of diabetes on patients undergoing robotic major hepatectomy. With Institutional Review Board (IRB) approval, 94 patients undergoing major hepatectomy were prospectively followed. Demographic data and postoperative outcomes were analyzed and compared between diabetic and non-diabetic patients. Data were presented as median (mean ± SD). Patients were of age 62 (61 ± 13.0) years, BMI of 29 (29 ± 5.9) kg/m2, and ASA class of 3 (3 ± 0.55). The mass size was 5 (5 ± 3.0) cm. Operative duration was 252 (277 ± 106.6) min with estimated blood loss (EBL) was 175 (249 ± 275.9) mL. One operation was converted to 'open' due to bleeding, accounting for one intraoperative complication. Postoperatively, nine patients required ICU admission, with a duration of 1 (4 ± 5.9) day. Seven patients had postoperative complications. Length of stay (LOS) was 4 (4 ± 2.6) days. Fourteen patients were readmitted within 30 days. There were no deaths in-hospital or within 30 days. Of the 94 patients, 22 were diabetic and 72 were nondiabetic. Diabetic patients were older (70 (69 ± 11.3) years versus 58 (58 ± 12.4) years (p = 0.004)). Intraoperatively, operative duration, EBL, and complications were not significantly different. Postoperatively, LOS, ICU admission, ICU duration, complications, in-hospital mortality, readmission in 30 days, and death after 30 days showed no significant difference between diabetics and nondiabetics. In our experience, diabetes has no significant effect on perioperative outcomes after a robotic major hepatectomy.
Assuntos
Diabetes Mellitus , Procedimentos Cirúrgicos Robóticos , Robótica , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Hepatectomia/efeitos adversos , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do TratamentoRESUMO
The present study used in vitro and in vivo stroke models to demonstrate the safety, efficacy, and mechanism of action of adult human bone marrow-derived NCS-01 cells. Coculture with NCS-01 cells protected primary rat cortical cells or human neural progenitor cells from oxygen glucose deprivation. Adult rats that were subjected to middle cerebral artery occlusion, transiently or permanently, and subsequently received intracarotid artery or intravenous transplants of NCS-01 cells displayed dose-dependent improvements in motor and neurological behaviors, and reductions in infarct area and peri-infarct cell loss, much better than intravenous administration. The optimal dose was 7.5 × 106 cells/mL when delivered via the intracarotid artery within 3 days poststroke, although therapeutic effects persisted even when administered at 1 week after stroke. Compared with other mesenchymal stem cells, NCS-01 cells ameliorated both the structural and functional deficits after stroke through a broad therapeutic window. NCS-01 cells secreted therapeutic molecules, such as basic fibroblast growth factor and interleukin-6, but equally importantly we observed for the first time the formation of filopodia by NCS-01 cells under stroke conditions, characterized by cadherin-positive processes extending from the stem cells toward the ischemic cells. Collectively, the present efficacy readouts and the novel filopodia-mediated mechanism of action provide solid lab-to-clinic evidence supporting the use of NCS-01 cells for treatment of stroke in the clinical setting.
Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , AVC Isquêmico/terapia , Transplante de Células-Tronco/métodos , Animais , Medula Óssea , Humanos , AVC Isquêmico/patologia , Masculino , RatosRESUMO
AIMS: Hyperbaric oxygen therapy (HBOT) has been widely used as postinjury treatment; however, we investigate its ability to mitigate potential damage as a preconditioning option. Here, we tested the hypothesis that HBOT preconditioning mitigates cell death in primary rat neuronal cells (PRNCs) through the transfer of mitochondria from astrocytes. METHODS: Primary rat neuronal cells were subjected to a 90-minute HBOT treatment at 2.5 absolute atmospheres prior to either tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccharide (LPS) injury to simulate the inflammation-plagued secondary cell death associated with stroke and traumatic brain injury (TBI). After incubation with TNF-alpha or LPS, the cell viability of each group was examined. RESULTS: There was a significant increase of cell viability accompanied by mitochondrial transfer in the injury groups that received HBOT preconditioning compared to the injury alone groups (44 ± 5.2 vs 68 ± 4.48, n = 20, P < 0.05). The transfer of mitochondria directly after HBOT treatment was visualized by capturing images in 5-minute intervals, which revealed that the robust transfer of mitochondria begins soon after HBOT and persisted throughout the treatment. CONCLUSION: This study shows that HBOT preconditioning stands as a robust prophylactic treatment for sequestration of inflammation inherent in stroke and TBI, possibly facilitating the transfer of resilient mitochondria from astrocytes to inflammation-susceptible neuronal cells in mitigating cell death.
Assuntos
Oxigenoterapia Hiperbárica , Inflamação/terapia , Mitocôndrias/fisiologia , Animais , Lesões Encefálicas Traumáticas/terapia , Sobrevivência Celular , Células Cultivadas , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/terapiaRESUMO
Although hyperbaric oxygen therapy (HBOT) is common as a treatment for injuries, this study aimed to research the ability of HBOT in preconditioning to diminish any potential damage. The hypothesis stated that HBOT preconditioning alleviated the death of cells in primary rat neuronal cells (PRNCs) by transferring mitochondria from astrocytes. In this experiment, PRNCs were given an HBOT treatment before a tumor necrosis factor-alpha or lipopolysaccharide injury which resembled cell death associated with stroke and traumatic brain injury (TBI). After being examined, the study found more cell viability in the PRNCs that had received HBOT precondition and a mitochondrial transfer. The mitochondrial transfer was visualized by a series of images showing the transfer after the HBOT treatment. This study demonstrated the ability of HBOT preconditioning as a treatment for inflammation in stroke and TBI, with the transfer of mitochondria from astrocytes to PRNCs reducing cell death. Along with discussion of the study, this review also focuses on different stroke treatments in comparison with HBOT.
RESUMO
Cerebral ischemia and its pathological sequelae are responsible for severe neurological deficits generally attributed to the neural death within the infarcted tissue and adjacent regions. Distal brain regions, and even peripheral organs, may be subject to more subtle consequences of the primary ischemic event which can initiate parallel disease processes and promote comorbid symptomology. In order to characterize the susceptibility of cerebellar brain regions and the heart to transient global ischemia (TGI) in nonhuman primates (NHP), brain and heart tissues were harvested 6 months post-TGI injury. Immunostaining analysis with unbiased stereology revealed significant cell death in lobule III and IX of the TGI cerebellum when compared to sham cerebellum, coinciding with an increase in inflammatory and apoptotic markers. Cardiac tissue analysis showed similar increases in inflammatory and apoptotic cells within TGI hearts. A progressive inflammatory response and cell death within the cerebellum and heart of chronic TGI NHPs indicate secondary injury processes manifesting both centrally and peripherally. This understanding of distal disease processes of cerebral ischemia underscores the importance of the chronic aberrant inflammatory response and emphasizes the needs for therapeutic options tailored to target these pathways. Here, we discuss the protocols for characterizing the histopathological effects of transient global ischemia in nonhuman primate cerebellum and heart, with an emphasis on the inflammatory and apoptotic cell death processes.
Assuntos
Isquemia Encefálica/metabolismo , Morte Celular , Cerebelo/irrigação sanguínea , Isquemia Miocárdica/metabolismo , Animais , Biomarcadores , Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Cerebelo/patologia , Modelos Animais de Doenças , Imunofluorescência/métodos , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/patologiaRESUMO
Traumatic brain injury (TBI) displays cognitive and motor symptoms following the initial injury which can be exacerbated by secondary cell death. Aging contributes significantly to the morbidity of TBI, with higher rates of negative neurological and behaviors outcomes. In the recent study, young and aged animals were injected intravenously with human adipose-derived mesenchymal stem cells (hADSCs) (Tx), conditioned media (CM), or vehicle (unconditioned media) following TBI. The beneficial effects of hADSCs were analyzed using various molecular and behavioral techniques. More specially, DiR-labeled hADSCs were used to observe the biodistribution of the transplanted cells. In addition, a battery of behavior tests was conducted to evaluate the neuromotor function for each treatment group and various regions of the brain were analyzed utilizing Nissl, hematoxylin and eosin (H&E), and human nuclei (HuNu) staining. Finally, flow cytometry was also performed to determine the levels of various proteins in the spleen. Here, we discuss the protocols for characterizing the histopathological and behavioral effects of transplanted stem cells in an animal model of TBI, with an emphasis on the role of aging in the therapeutic outcomes.
Assuntos
Envelhecimento/patologia , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/terapia , Animais , Lesões Encefálicas Traumáticas/fisiopatologia , Humanos , Aprendizagem , Transplante de Células-Tronco Mesenquimais , RatosRESUMO
International Stem Cell Corporation human parthenogenetic neural stem cells (ISC-hpNSC) have potential therapeutic value for patients suffering from traumatic brain injury (TBI). Here, we demonstrate the behavioral and histological effects of transplanting ISC-hpNSC intracerebrally in an animal model of TBI. Methods: Sprague-Dawley rats underwent a moderate controlled cortical impact TBI surgery. Transplantation occurred at 72 h post-TBI with functional readouts of behavioral and histological deficits conducted during the subsequent 3-month period after TBI. We characterized locomotor, neurological, and cognitive performance at baseline (before TBI), then on days 0, 1, 7, 14, 30, 60, and 90 (locomotor and neurological), and on days 28-30, 58-60, and 88-90 (cognitive) after TBI. Following completion of behavioral testing at 3 months post-TBI, animals were euthanized by transcardial perfusion and brains harvested to histologically characterize the extent of brain damage. Neuronal survival was revealed by Nissl staining, and stem cell engraftment and host tissue repair mechanisms such as the anti-inflammatory response in peri-TBI lesion areas were examined by immunohistochemical analyses. Results: We observed that TBI groups given high and moderate doses of ISC-hpNSC had an improved swing bias on an elevated body swing test for motor function, increased scores on forelimb akinesia and paw grasp neurological tests, and committed significantly fewer errors on a radial arm water maze test for cognition. Furthermore, histological analyses indicated that high and moderate doses of stem cells increased the expression of phenotypic markers related to the neural lineage and myelination and decreased reactive gliosis and inflammation in the brain, increased neuronal survival in the peri-impact area of the cortex, and decreased inflammation in the spleen at 90 days post-TBI. Conclusion: These results provide evidence that high and moderate doses of ISC-hpNSC ameliorate TBI-associated histological alterations and motor, neurological, and cognitive deficits.
Assuntos
Lesões Encefálicas Traumáticas/terapia , Regeneração do Cérebro , Células-Tronco Neurais/fisiologia , Transplante de Células-Tronco/métodos , Animais , Cognição , Modelos Animais de Doenças , Humanos , Locomoção , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
Stroke is a major cause of death and disability in the United States and around the world with limited therapeutic option. Here, we discuss the critical role of mitochondria in stem cell-mediated rescue of stroke brain by highlighting the concept that deleting the mitochondria from stem cells abolishes the cells' regenerative potency. The application of innovative approaches entailing generation of mitochondria-voided stem cells as well as pharmacological inhibition of mitochondrial function may elucidate the mechanism underlying transfer of healthy mitochondria to ischemic cells, thereby providing key insights in the pathology and treatment of stroke and other brain disorders plagued with mitochondrial dysfunctions.
Assuntos
Encéfalo/metabolismo , Mitocôndrias , Células-Tronco/metabolismo , Acidente Vascular Cerebral , Animais , Encéfalo/patologia , Modelos Animais de Doenças , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/transplante , Ratos , Ratos Sprague-Dawley , Células-Tronco/patologia , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/terapiaRESUMO
Brain insults with progressive neurodegeneration are inherent in pathological symptoms that represent many psychiatric illnesses. Neural network disruptions characterized by impaired neurogenesis have been recognized to precede, accompany, and possibly even exacerbate the evolution and progression of symptoms of psychiatric disorders. Here, we focus on the neurodegeneration and the resulting psychiatric symptoms observed in fetal alcohol spectrum disorder and epilepsy, in an effort to show that these two diseases are candidate targets for stem cell therapy. In particular, we provide preclinical evidence in the transplantation of neural stem cells (NSCs) in both conditions, highlighting the potential of this cell-based treatment for correcting the psychiatric symptoms that plague these two disorders. Additionally, we discuss the challenges of NSC transplantation and offer insights into the mechanisms that may mediate the therapeutic benefits and can be exploited to overcome the hurdles of translating this therapy from the laboratory to the clinic. Our ultimate goal is to advance stem cell therapy for the treatment of psychiatric disorders.