Limbal stem cell therapy.

PURPOSE OF REVIEW: To highlight the progress and future direction of limbal stem cell (LSC) therapies for the treatment of limbal stem cell deficiency (LSCD). RECENT FINDINGS: Direct LSC transplantation have demonstrated good long-term outcomes. Cultivated limbal epithelial transplantation (CLET) has been an alternative to treat severe to total LSCD aiming to improve the safety and efficacy of the LSC transplant. A prospective early-stage uncontrolled clinical trial shows the feasibility and safety of CLET manufactured under xenobiotic free conditions. Other cell sources for repopulating of the corneal epithelium such as mesenchymal stem cells (MSCs) and induced pluripotent stem cells are being investigated. The first clinical trials of using MSCs showed short-term results, but long-term efficacy seems to be disappointing. A better understanding of the niche function and regulation of LSC survival and proliferation will lead to the development of medical therapies to rejuvenate the residual LSCs found in a majority of eyes with LSCD in vivo. Prior efforts have been largely focused on improving LSC transplantation. Additional effort should be placed on improving the accuracy of diagnosis and staging of LSCD, and implementing standardized outcome measures which enable comparison of efficacy of different LSCD treatments for different severity of LSCD. The choice of LSCD treatment will be customized based on the severity of LSCD in the future. SUMMARY: New approaches for managing different stages of LSCD are being developed. This concise review summarizes the progresses in LSC therapies for LSCD, underlying mechanisms, limitations, and future areas of development.

[Mixed adenoneuroendocrine carcinoma: case report]. / Carcinoma adenoneuroendocrino mixto: reporte de caso.

Introducción: Mixed adenoneuroendocrine carcinoma is a rare tumor of the gastrointestinal tract with double differentiation into adenomatous and neuroendocrine carcinoma, each component with at least 30%. Case report: A 60-year-old female with acute abdominal pain. Surgical treatment was decided, finding a tumor at the level of the cecum and ascending colon, a right hemicolectomy and ileostomy were performed. Discussion: Mixed adenoneuroendocrine carcinoma can appear in various organs. They are highly malignant tumors, with a high risk of metastasis. Conclusions: These tumors do not present symptoms or specific radiological or laboratory findings; diagnosis depends on postoperative histopathological and immunohistochemical studies.

Introducción: El carcinoma adenoneuroendocrino mixto es un tumor raro del tracto gastrointestinal con doble diferenciación en carcinoma adenomatoso y neuroendocrino, cada componente con al menos el 30%. Caso clínico: Mujer de 60 años con cuadro de dolor abdominal agudo. Se decide tratamiento quirúrgico, encontrando un tumor a nivel de ciego y colon ascendente, y se realizan hemicolectomía derecha e ileostomía. Discusión: El carcinoma adenoneuroendocrino mixto puede aparecer en diversos órganos. Son tumores muy malignos, con alto riesgo de metástasis. Conclusiones: Estos tumores no presentan síntomas ni hallazgos radiológicos o de laboratorio específicos; el diagnóstico depende de estudios histopatológicos e inmunohistoquímicos posoperatorios.

Late-onset rupture of an intracranial dermoid cyst: a case report.

BACKGROUND: Dermoid cysts are developmental abnormalities occurring between the third and fifth week of embryogenesis. These lesions can initially develop as intracranial or extracranial and persist throughout the patient's lifetime. While generally benign, their symptoms can be due to mass effect or local irritation secondary to rupture and release of contents, typically presenting as headaches and seizures. Intracranial dermoid cysts are rare and comprise less than 1% of all intracranial lesions, with rupture occurring approximately 0.18% of the time. CASE PRESENTATION: Our case describes a 42-year-old Hispanic female with a late-onset rupture of an intracranial dermoid cyst with associated new onset seizures. She underwent uncomplicated neurosurgical resection with mesh placement and was scheduled to follow-up as an outpatient. CONCLUSION: To avoid rupture and associated sequelae in future patients, we recommend considering a more invasive approach as the initial strategy if internal cysts are relatively accessible.

Wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency.

Limbal epithelial stem/progenitor cells (LSCs) are adult stem cells located at the limbus, tightly regulated by their niche involving numerous signaling pathways, such as Wnt. Wnt proteins are secreted morphogens that play critical roles in embryonic development, stem cell proliferation, self-renewal, tissue regeneration, and remodeling in adults. It has been shown that a small molecule Wnt mimic could improve LSCs expansion ex vivo. Damage to the LSCs and/or their niche can lead to limbal stem cell deficiency (LSCD), a condition that can cause corneal blindness and is difficult to treat. This study explored if repopulating residual LSCs in partial LSCD through Wnt activation could be a novel therapeutic approach. To mimic LSCD due to a chemical injury, single cultured LSCs were exposed to various concentrations of sodium hydroxide. A progressive loss of the LSCs phenotype was observed: the percentage of p63bright cells and cytokeratin (K)14+ cells decreased while the percentage of K12+ increased. Wnt activation was attained by treating the LSCs with lithium chloride (LiCl) and a small-molecule Wnt mimic, respectively. After 18 h of treatment, LSCs proliferation was increased, and the LSCs phenotype was recovered, while the untreated cells did not proliferate and lost their phenotype. The percentage of p63bright cells was significantly higher in the Wnt mimic-treated cells compared with untreated cells, while the percentage of K12+ cells was significantly lower. These findings suggest that local Wnt activation may rescue LSCs upon alkaline injury.

Ocular Surface Regeneration by Limbal Stem Cells Therapies: State of the Art, Challenges, and Perspectives.

Limbal stem cells (LSCs) are adult stem cells located at the limbus ensuring the continuous renewal of the corneal epithelium, critical to maintain an optimal visual function. Damages to the LSCs or their niche microenvironment lead to limbal stem cell deficiency (LSCD), a potentially blinding disease. Transplantation of LSCs as a treatment for severe to total LSCD has gained popularity since 1980s, owing to the clinical success of the first direct limbal autograft transplantation. Recent advances in the understanding of the LSCs' molecular identity and regulation have enabled preclinical and clinical advancements of promising LSCs therapies. However, lack of standardization of the diagnostic methods, staging of the disease severity, manufacturing process, and clinical outcome measures have hindered the advancement of the therapy. To move these therapies to the clinic, optimization and standardization of the diagnostic strategy, cell product manufacturing, and assessment of clinical efficacy with potency assays are key points to the development of customized therapies. Recent findings suggest that residual LSCs exist in eyes presenting with clinical signs of total LSCD, which opens new therapeutic strategies for eyes with partial LSCD. Prospective, randomized, multicentric controlled clinical trials are necessary to determine the efficacy of different LSCs therapies for different stages of LSCD using a set of standardized outcome measures.

Single mRNA detection of Wnt signaling pathway in the human limbus.

Limbal epithelial stem/progenitor cells (LSCs) are adult stem cells located at the limbus, tightly regulated by their close microenvironment. It has been shown that Wnt signaling pathway is crucial for LSCs regulation. Previous differential gene profiling studies confirmed the preferential expression of specific Wnt ligands (WNT2, WNT6, WNT11, WNT16) and Wnt inhibitors (DKK1, SFRP5, WIF1, FRZB) in the limbal region compared to the cornea. Among all frizzled receptors, frizzled7 (Fzd7) was found to be preferentially expressed in the basal limbal epithelium. However, the exact localization of Wnt signaling molecules-producing cells in the limbus remains unknown. The current study aims to evaluate the in situ spatial expression of these 4 Wnt ligands, 4 Wnt inhibitors, and Fzd7. Wnt ligands, DKK1, and Fzd7 expression were scattered within the limbal epithelium, at a higher abundance in the basal layer than the superficial layer. SFRP5 expression was diffuse among the limbal epithelium, whereas WIF1 and FRZB expression was clustered at the basal limbal epithelial layer corresponding to the areas of high levels of Fzd7 expression. Quantitation of the fluorescence intensity showed that all 4 Wnt ligands, 3 Wnt inhibitors (WIF1, DKK1, FRZB), and Fzd7 were highly expressed at the basal layer of the limbus, then in a decreasing gradient toward the superficial layer (P < 0.05). The expression levels of all 4 Wnt ligands, FRZB, and Fzd7 in the basal epithelial layer were higher in the limbus than the central cornea (P < 0.05). All 4 Wnt ligands, 4 Wnt inhibitors, and Fzd7 were also highly expressed in the limbal stroma immediately below the epithelium but not in the corneal stroma (P < 0.05). In addition, Fzd7 had a preferential expression in the superior limbus compared to other limbal quadrants (P < 0.05). Taken together, the unique expression patterns of the Wnt molecules in the limbus suggests the involvement of both paracrine and autocrine effects in LSCs regulation, and a fine balance between Wnt activators and inhibitors to govern LSC fate.

Changing characteristics of emergency surgery during COVID-19 pandemic: a retrospective cohort study.

BACKGROUND: In other countries, researchers have noticed diverse variations in the features of patients undergoing emergency surgery during the COVID-19 pandemic. In Mexico, there is not information about this issue. METHODS: Workers of the Mexican Government, who required emergency surgeries were studied by the general surgery service of a General Hospital administered by the Institute of Social Security and Services for State Workers Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), through the periods from March-August 2019 (non-exposed) and March-August 2020 (exposed). The analysis included: demographic data, laboratory information, post-operative diagnoses, symptoms' length, days of emergency stay, and post-operative stay. RESULTS: One hundred and ninety-three emergency surgeries were analyzed; 106 in 2019 and 87 in 2020 (a decrease of 18%). Throughout the pandemic, the number of days between the symptoms' onset and surgery was greater: 2019, 7.6 ± 4.6 days; 2020, 14 ± 6.7 days (p < 0.0001). In addition, cases of acute appendicitis decreased (2019-60.3%; 2020-42.5%), and those of acute calculous cholecystitis increased (2019-12.2%; 2020-24.1%). CONCLUSION: Through the COVID-19 pandemic, there were notable changes in the characteristics of Mexican Government's workers who warranted emergency surgery.

ANTECEDENTES: En otros países, han notado diversos cambios en las características de los pacientes sometidos a cirugía de emergencia durante la pandemia de COVID-19. En México no existe información sobre este tema. MÉTODO: Estudiamos a los trabajadores del gobierno mexicano que requirieron tratamiento quirúrgico de emergencia por el servicio de cirugía general de un Hospital General del Instituto de Seguridad y Servicios Sociales para los Trabajadores del Estado (ISSSTE), durante los periodos de marzo-agosto de 2019 (no expuestos) y marzo-agosto de 2020 (expuestos). El análisis incluyó: datos demográficos, datos de laboratorio, diagnósticos postoperatorios, duración de los síntomas, días de estancia en emergencias y estadía postoperatoria. RESULTADOS: Se analizaron 193 cirugías de emergencia; 106 en 2019 y 87 en 2020 (una disminución del 18%). En la pandemia, el número de días entre el inicio de los síntomas y la cirugía fue mayor: 2019, 7.6 ± 4.6 días; 2020, 14 ± 6.7 días (p < 0.0001). Además, disminuyeron los casos de apendicitis aguda (2019-60,3%; 2020-42,5%) y aumentaron los de colecistitis litiásica aguda (2019-12,2%; 2020-24,1%). CONCLUSIÓN: Durante la pandemia de COVID-19, hubo cambios notables en las características de los trabajadores del gobierno mexicano que ameritaron cirugías de emergencia.

Presentación polipoide de un tumor neuroendocrino: reporte de caso y revisión de la literatura / Neuroendocrine Tumor Polypoid Presentation: Case Report and Literature Review

Resumen Debido a la implementación de las colonoscopias como método de tamizaje, ha aumentado el diagnóstico de tumores neuroendocrinos rectales (TNER), la mayoría tiene un tamaño menor de 1 centímetro en el momento del diagnóstico, confinado a la submucosa y bien diferenciado; generalmente tienen un curso benigno y en su mayoría se tratan por métodos endoscópicos. Las metástasis son raras y dependen del tamaño tumoral y otros factores como la invasión a la submucosa, diseminación linfática y clasificación histológica, lo cual determinará el pronóstico y tratamiento a elección. Se presenta el caso de un tumor neuroendocrino rectal presentado en forma de pólipo durante un tamizaje endoscópico de rutina y una aproximación de la literatura actual.

Abstract Diagnosis of rectal neuroendocrine tumor (NET) has increased due to the implementation of colonoscopies as a screening method. Most rectal NETs are less than 1cm at diagnosis time, confined to the submucosa, and well differentiated. They generally have a benign course and are treated mainly using endoscopic methods. Metastases are rare and depend on tumor size and other factors such as submucosal invasion, lymphatic spread, and histologic classification, which will determine the prognosis and treatment. We present a case of a rectal neuroendocrine tumor as a polyp during routine endoscopic screening and a review of the current literature.

Septic Arthritis With Superimposed Acute Gouty Arthritis in a Rheumatoid Arthritis Patient.

Septic arthritis is a rare but serious complication of both rheumatoid and gouty arthritis and can lead to significant morbidity and even mortality. Here, we report a case of septic arthritis with bacteremia, monosodium urate crystals, and hyperuricemia in a 75-year-old male with long-standing rheumatoid arthritis. Arthrocentesis revealed gram-positive cocci representing group B streptococcus (Streptococcus agalactiae) infection and monosodium urate crystals. A diagnosis of septic arthritis with superimposed acute gouty arthritis was made and the patient was treated accordingly. Management included surgical irrigation and debridement, antibiotic therapy, and systemic glucocorticoids which resulted in a significant improvement in the patient's clinical status.

Infarto omental como causa inusual de dolor abdominal: un reporte de caso / Omental infarction as an unusual cause of abdominal pain: a case report

Resumen El infarto omental es una causa infrecuente de abdomen agudo y de etiología no muy conocida, su presentación clínica inespecífica puede simular otras patologías más comunes, lo que hace su diagnóstico un reto clínico. Se presenta el caso de una mujer de 33 años que asiste a urgencias con clínica de dolor abdominal agudo, atípico, con hallazgos ecográficos sugestivos de apendicitis aguda, sin embargo, por la clínica inusual se realizó tomografía axial computarizada (TAC) de abdomen, con reporte sugestivo de diverticulitis. Ante la no concordancia clínica ni imagenológica, la paciente fue llevada a laparoscopia diagnóstica, como hallazgo intraoperatorio se evidenció isquemia del epiplón como único hallazgo, por lo cual se realizó omentectomía parcial. Siendo este un caso de importancia clínica debido a que el infarto omental debe considerarse entre los diagnósticos diferenciales de dolor abdominal agudo, en especial cuando la presentación es atípica y se han excluido las patologías más frecuentes. MÉD.UIS.2022;35(1): 43-8.

Abstract Omental infarction is an uncommon cause of acute abdomen and its etiology is not well known. Its nonspecific clinical presentation can simulate bibr more common pathologies which makes its diagnosis a clinical challenge. We present the case of a 33-year-old woman who attends the emergency room with symptoms of acute, atypical abdominal pain, ultrasound findings were suggestive of acute appendicitis, however, due to unusual symptoms, a computerized axial tomography (CT) of the abdomen was performed, with a suggestive report of diverticulitis. Given the clinical and imagenologycal findings mismatch, the patient underwent to diagnostic laparoscopy where omentum ischemia was evidenced as the only finding, partial omentectomy was performed. This is a case of clinical importance because the omental infarction should be considered among the differential diagnoses of acute abdominal pain, especially when the presentation is atypical and the most frequent pathologies have been excluded. MÉD.UIS.2022;35(1): 43-8.

The Role of Serial Imaging in Neurocysticercosis for Disease Resolution.

Neurocysticercosis (NCC), the most common parasitic infection of the CNS in humans, is a frequent cause of seizure disorders and epilepsy. The cystic larvae Taenia solium is endemic to developing countries where the population raises pigs as a reliable source of food, however, massive immigration has now forced the surge of the disease in developed areas making it a worldwide problem. Clinical presentation is affected by the size, number, and location of the lesions within the brain, with the most common manifestations being seizures, headaches, and increased intracranial pressure. The appearance of NCC on radiological imaging helps determine the stage of the disease, required for appropriate antiparasitic treatment. In this article, we detail the case of a patient who presented for recurrent seizures after reportedly undergoing treatment for NCC years prior.

Partial Thrombosis of Inferior Mesenteric Vein With Thrombophlebitis.

Inferior mesenteric vein thrombosis (IMVT) is a rare entity that can lead to a potentially lethal event unless recognized early in the disease. Although its prevalence is low, IMVT presents mainly in certain conditions such as in inflammatory processes like diverticulitis, arrhythmias, hypercoagulable states, connective tissue disorders, malignancy, or hereditary thrombophilias.  Mesenteric venous thrombophlebitis is a condition in which a blood clot in a vein causes inflammation and pain. It can appear in an acute or subacute manner that leads to acute mesenteric ischemia. The case of a 58-year-old male without a significant past medical history who presented with suprapubic abdominal pain secondary to a partial IMVT of unknown etiology with accompanying thrombophlebitis is discussed here.

An Incidental Discovery Following Hypertension and Headaches: A Pheochromocytoma Case Report.

Pheochromocytomas (PCC) are rare neuroendocrine tumors of the adrenal medulla that arise from chromaffin cells. These cells are neural crest derivatives and are innervated by the splanchnic nerve of the sympathetic nervous system which releases acetylcholine that in turn binds to nicotinic acetylcholine receptors of the adrenal medulla causing the release of catecholamines. The dopamine, norepinephrine, and epinephrine released from these tumors are responsible for the episodic hyperadrenergic symptoms seen in these cases such as hypertension, palpitations, and headaches. This case report discusses the incidental finding of a unilateral PCC in a 58-year-old woman who initially presented to our emergency department complaining of intermittent chest pain and headaches for two days.

Human limbal epithelial stem cell regulation, bioengineering and function.

The corneal epithelium is continuously renewed by limbal stem/progenitor cells (LSCs), a cell population harbored in a highly regulated niche located at the limbus. Dysfunction and/or loss of LSCs and their niche cause limbal stem cell deficiency (LSCD), a disease that is marked by invasion of conjunctival epithelium into the cornea and results in failure of epithelial wound healing. Corneal opacity, pain, loss of vision, and blindness are the consequences of LSCD. Successful treatment of LSCD depends on accurate diagnosis and staging of the disease and requires restoration of functional LSCs and their niche. This review highlights the major advances in the identification of potential LSC biomarkers and components of the LSC niche, understanding of LSC regulation, methods and regulatory standards in bioengineering of LSCs, and diagnosis and staging of LSCD. Overall, this review presents key points for researchers and clinicians alike to consider in deepening the understanding of LSC biology and improving LSCD therapies.

Role of Jagged1-mediated Notch Signaling Activation in the Differentiation and Stratification of the Human Limbal Epithelium.

The Notch signaling pathway plays a key role in proliferation and differentiation. We investigated the effect of Jagged 1 (Jag1)-mediated Notch signaling activation in the human limbal stem/progenitor cell (LSC) population and the stratification of the limbal epithelium in vitro. After Notch signaling activation, there was a reduction in the amount of the stem/progenitor cell population, epithelial stratification, and expression of proliferation markers. There was also an increase of the corneal epithelial differentiation. In the presence of Jag1, asymmetric divisions were decreased, and the expression pattern of the polarity protein Par3, normally present at the apical-lateral membrane of basal cells, was dispersed in the cells. We propose a mechanism in which Notch activation by Jag1 decreases p63 expression at the basal layer, which in turn reduces stratification by decreasing the number of asymmetric divisions and increases differentiation.

Expansion of Human Limbal Epithelial Stem/Progenitor Cells Using Different Human Sera: A Multivariate Statistical Analysis.

Transplantation of human cultured limbal epithelial stem/progenitor cells (LESCs) has demonstrated to restore the integrity and functionality of the corneal surface in about 76% of patients with limbal stem cell deficiency. However, there are different protocols for the expansion of LESCs, and many of them use xenogeneic products, being a risk for the patients' health. We compared the culture of limbal explants on the denuded amniotic membrane in the culture medium-supplemental hormone epithelial medium (SHEM)-supplemented with FBS or two differently produced human sera. Cell morphology, cell size, cell growth rate, and the expression level of differentiation and putative stem cell markers were examined. Several bioactive molecules were quantified in the human sera. In a novel approach, we performed a multivariate statistical analysis of data to investigate the culture factors, such as differently expressed molecules of human sera that specifically influence the cell phenotype. Our results showed that limbal cells cultured with human sera grew faster and contained similar amounts of small-sized cells, higher expression of the protein p63α, and lower of cytokeratin K12 than FBS cultures, thus, maintaining the stem/progenitor phenotype of LESCs. Furthermore, the multivariate analysis provided much data to better understand the obtaining of different cell phenotypes as a consequence of the use of different culture methodologies or different culture components.

Aedes aegypti Ir8a mutant female mosquitoes show increased attraction to standing water.

The detection of water sources is crucial for insects such as mosquitoes to avoid desiccation and survive. In addition, mosquitoes use humidity cues to successfully navigate the environment to find a suitable oviposition site. Previous studies have implicated some members of the ionotropic receptor family in humidity sensing by Drosophila. Here, we investigate if IR8a co-receptor mediates water detection in Aedes aegypti mosquitoes. Using a simple behavioral assay, we examined the attraction of Ir8a mutant mosquitoes to standing water. Ir8a mutant mosquitoes were able to discriminate between traps containing water and those without as well as wild-type and heterozygous control females. Surprisingly, the female mutants were more robustly drawn to standing water than control mosquitoes. Further investigation revealed that the increased behavioral attraction to water is likely not mediated by a metabolic need or an activity defect.

Notch Inhibition Prevents Differentiation of Human Limbal Stem/Progenitor Cells in vitro.

Notch signaling has been shown to regulate the homeostasis and wound healing of the corneal epithelium. We investigated the effect of Notch inhibition in the human limbal stem/progenitor cells (LSCs) in vitro by using small molecules. Treatment of the LSCs with DAPT and SAHM1 reduced the proliferation rate and maintained the undifferentiated state of the LSCs in a concentration dependent manner. Stratification and differentiation of the corneal epithelium were not reduced after Notch inhibition, indicating that the function of the corneal basal cells is retained. Our findings suggest that Notch signaling plays a role in the proliferation and maintenance of LSCs.

Aedes aegypti Mosquitoes Detect Acidic Volatiles Found in Human Odor Using the IR8a Pathway.

Mosquitoes use olfaction as a primary means of detecting their hosts. Previously, the functional ablation of a family of Aedes aegypti olfactory receptors, the odorant receptors (ORs), was not sufficient to reduce host seeking in the presence of carbon dioxide (CO2). This suggests the olfactory receptors that remain, such as the ionotropic receptors (IRs), could play a significant role in host detection. To test this, we disrupted the Ir8a co-receptor in Ae. aegypti using CRISPR/Cas9. We found that Ir8a mutant female mosquitoes are not attracted to lactic acid, a behaviorally active component of human sweat, and they lack odor-evoked responses to acidic volatiles. The loss of Ir8a reduces mosquito attraction to humans and their odor. We show that the CO2-detection pathway is necessary but not sufficient for IR8a to detect human odor. Our study reveals that the IR8a pathway is crucial for an anthropophilic vector mosquito to effectively seek hosts. VIDEO ABSTRACT.

Wnt Signaling Is Required for the Maintenance of Human Limbal Stem/Progenitor Cells In Vitro.

Purpose: A chemical approach to examine the role of Wnt signaling in maintaining the stemness and/or proliferation of limbal stem/progenitor cells (LSCs). Methods: LSCs were isolated from human donor eyes and cultured as single cells for 12 to 14 days with the following small molecules: IIIC3, an antagonist of the Wnt signaling inhibitor Dickkopf (DKK), and IC15, a Wnt signaling inhibitor. Proliferation of LSCs in the presence of IIIC3 and IC15 was determined by the number of cells and colonies established. Maintenance of stemness was determined by p63α, cytokeratin (K)12, and K14 expression. Results: Activation of Wnt, through IIIC3-mediated DKK inhibition, resulted in similar colony forming efficiency (CFE) as in the untreated LSCs, but significantly increased the number of cultivated cells 7.21% with 5 µM. Inhibition of Wnt with IC15 significantly reduced the CFE (P ≤ 0.01) and the number of cultivated cells by 16% to 29%. Percentage of cells expressing high levels of p63α (p63αbright) and quantity of small cells (≤12 µm), which contain the LSCs, increased 4.71% and 11.26% (both P < 0.05), respectively, with 5 µM IIIC3. All concentrations of IIIC3 and IC15 retained the K14 undifferentiated marker (97%), while differentiation, as detected by expression of K12, was found in up to 2% of cells in 1 µM IIIC3, 1 µM IC15, or 5 µM IIIC3. Conclusions: Wnt signaling is required in LSC proliferation and maintenance of an undifferentiated state. The current study is a proof of concept that the Wnt pathway could be modulated in LSCs to enhance or decrease the efficiency of human LSC expansion.