preclinical study

An increase in the accuracy of monitoring of glucose concentration indicators and an increase in the running time of glucose sensors are promising directions in the field of diabetology. One of the ways to extend the lifetime of a sensor is its complete implantation excluding direct communication with the skin surface. For effective long-term functioning in the patient’s body, the surface of an implantable sensor should be highly biocompatibile: it should not induce allergic and inflammatory reactions as well as the demarcation reaction (formation of a dense connective tissue capsule). Earlier, a group of authors developed a glucose-permeable membrane and a biocompatible coating comprising a complex of nadroparin with transesterified polyethylene glycol and γ-aminopropyl triethoxysilane, which formed a protein repellent hydrogel on the membrane surface. Aims. To evaluate the biocompatibility of the experimental coated membrane implanted into laboratory animals. Methods. The experime...

Localized vascular disruption after traumatic spinal cord injury (SCI) triggers a cascade of secondary events, including inflammation, gliosis, and scarring, that can further impact recovery. In addition to immunomodulatory and neurotrophic properties, mesenchymal stromal cells (MSCs) possess pericytic characteristics. These features make MSCs an ideal candidate for acute cell therapy targeting vascular disruption, which could reduce the severity of secondary injury, enhance tissue preservation and repair, and ultimately promote functional recovery. A moderately severe cervical clip compression/contusion injury was induced at C7-T1 in adult female rats, followed by an intravenous tail vein infusion 1 hour post-SCI of (a) term-birth human umbilical cord perivascular cells (HUCPVCs); (b) first-trimester human umbilical cord perivascular cells (FTM HUCPVCs); (c) adult bone marrow mesenchymal stem cells; or (d) vehicle control. Weekly behavioral testing was performed. Rats were sacrific...

Discrepancies in preclinical studies of aspirin (ASA) antiplatelet activity in mouse models of bleeding and arterial thrombosis led us to evaluate commonly reported methods in order to propose a procedure for reliably measuring the effects of single dose ASA on mouse hemostasis. FVB and C57Bl6 mice received 100 mg/kg of ASA or vehicle orally 30 min or 3 h prior to investigate either hemostasis using the tail bleeding assay or carotid thrombosis induced by FeCl 3 , or to blood sampling for isolated platelet aggregation and TXB 2 generation. Expected inhibition of COX1 by ASA was ascertained by a strong decrease in TXB 2 production, and its effect on platelet function and hemostasis, by decreased collagen-induced aggregation and increased bleeding time, respectively. Strikingly, we determined that anti-hemostatic effects of ASA were more predictable 30 min after administration than 3 h later. Conversely, ASA did not alter time to arterial occlusion of the carotid upon FeCl 3-induced thrombosis, suggesting ASA not to be used as reference inhibitor drug in this model of arterial thrombosis.

Discrepancies in preclinical studies of aspirin (ASA) antiplatelet activity in mouse models of bleeding and arterial thrombosis led us to evaluate commonly reported methods in order to propose a procedure for reliably measuring the effects of single dose ASA on mouse hemostasis. FVB and C57Bl6 mice received 100 mg/kg of ASA or vehicle orally 30 min or 3 h prior to investigate either hemostasis using the tail bleeding assay or carotid thrombosis induced by FeCl 3 , or to blood sampling for isolated platelet aggregation and TXB 2 generation. Expected inhibition of COX1 by ASA was ascertained by a strong decrease in TXB 2 production, and its effect on platelet function and hemostasis, by decreased collagen-induced aggregation and increased bleeding time, respectively. Strikingly, we determined that anti-hemostatic effects of ASA were more predictable 30 min after administration than 3 h later. Conversely, ASA did not alter time to arterial occlusion of the carotid upon FeCl 3-induced thrombosis, suggesting ASA not to be used as reference inhibitor drug in this model of arterial thrombosis.

Background: Menstrual blood-derived stem cells (MenSCs) are a novel source of stem cells that can be easily isolated non-invasively from female volunteered donor without ethical consideration. These mesenchymal-like stem cells have high rate of proliferation and possess multi lineage differentiation potency. This study was undertaken to isolate the MenSCs and assess their potential in differentiation into epidermal lineage. Methods: About 5-10 ml of menstrual blood (MB) was collected using sterile Diva cups inserted into vagina during menstruation from volunteered healthy fertile women aged between 22-30 years. MB was transferred into Falcon tubes containing phosphate buffered saline (PBS) without Ca2(+) or Mg2(+) supplemented with 2.5 µg/ml fungizone, 100 µg/mL streptomycin, 100 U/mL penicillin and 0.5 mM EDTA. Mononuclear cells were separated using Ficoll-Hypaque density gradient centrifugation and washed out in PBS. The cell pellet was suspended in DMEM-F12 medium supplemented with 10% FBS and cultured in tissue culture plates. The isolated cells were co-cultured with keratinocytes derived from the foreskin of healthy newborn male aged 2-10 months who was a candidate for circumcision for differentiation into epidermal lineage. Results: The isolated MenSCs were adhered to the plate and exhibited spindle-shaped morphology. Flow cytometric analysis revealed the expression of mesenchymal markers of CD10, CD29, CD73, and CD105 and lack of hematopoietic stem cells markers. An early success in derivation of epidermal lineage from MenSCs was visible. Conclusion: The MenSCs are a real source to design differentiation to epidermal cells that can be used non-invasively in various dermatological lesions and diseases.

Rheumatoid arthritis is a chronic inflammatory and systemic autoimmune disease characterized by joint pain, swelling and stiffness. Inflammatory mediators such as pro-inflammatory cytokines, IL-6, COX-2, TNFalpha, etc. attack joints upon activation and generate reactive oxygen/nitrogen species, causing oxidative stress. High risk of opportunistic infections has also been reported in patients associated with the use of TNF-α inhibitors, corticosteroids and methotrexate drugs. Use of herbal medicine is becoming popular due to their negligible toxicity and rare side effects. The present study emphasizes the use of a bioprospection model which includes random search, priority indexing and rationale based selection of natural plant products targeting key descriptors of the disease. The identified plants could be used as nutraceuticals to ameliorate the vulnerable condition in inflammatory disorder(s). Further in vitro and in vivo analysis is also warranted, so as to validate the findings...

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X211035625 for Preclinical <i>in vivo</i> longitudinal assessment of KG207-M as a disease-modifying Alzheimer's disease therapeutic by Min Su Kang, Monica Shin, Julie Ottoy, Arturo Aliaga Aliaga, Sulantha Mathotaarachchi, Kely Quispialaya, Tharick A Pascoal, D Louis Collins, M. Mallar Chakravarty, Axel Mathieu, Åsa Sandelius, Kaj Blennow, Henrik Zetterberg, Gassan Massarweh, Jean-Paul Soucy, A Claudio Cuello, Serge Gauthier, Michael Waterston, Nathan Yoganathan, Etienne Lessard, Arsalan Haqqani, Kerry Rennie, Danica Stanimirovic, Balu Chakravarthy and Pedro Rosa-Neto in Journal of Cerebral Blood Flow & Metabolism

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X211035625 for Preclinical <i>in vivo</i> longitudinal assessment of KG207-M as a disease-modifying Alzheimer's disease therapeutic by Min Su Kang, Monica Shin, Julie Ottoy, Arturo Aliaga Aliaga, Sulantha Mathotaarachchi, Kely Quispialaya, Tharick A Pascoal, D Louis Collins, M. Mallar Chakravarty, Axel Mathieu, Åsa Sandelius, Kaj Blennow, Henrik Zetterberg, Gassan Massarweh, Jean-Paul Soucy, A Claudio Cuello, Serge Gauthier, Michael Waterston, Nathan Yoganathan, Etienne Lessard, Arsalan Haqqani, Kerry Rennie, Danica Stanimirovic, Balu Chakravarthy and Pedro Rosa-Neto in Journal of Cerebral Blood Flow & Metabolism

Several studies have shown that mesenchymal stromal/stem cells (MSCs) exert their neuroprotective and neurorestorative efficacy via the secretion of neurotrophic factors. Based on these studies, many clinical trials using MSCs for the treatment of neurological disorders have been conducted, and results regarding their feasibility and efficacy have been reported. The present review aims to highlight the characteristics and basic research regarding the role of MSCs in neurological disease and to discuss the recent progress in clinical trials using MSCs to treat various neurological disorders.

Bone marrow mesenchymal stem cells can differentiate into neurons and astrocytes after transplantation in the spinal cord injury of rats. Although bone marrow mesenchymal stem cells are known to protect against spinal cord injury through anti-apoptotic effects, but generation of neural stem cells with large number and safety protocols unclear. In the present study, described the differentiation of bone marrow stromal cells (BMSC) into a neural stem cell-like under the influence of a factor inducing non-toxic bioactive substance TNT.In the present study, bone marrow mesenchymal stem cells were cultured and proliferated, then induced with bioactive substance TNT. That these cells differentiate as a neurospherelike structures and neural stem cells. These cells approved by immunocytochemistry and RT-PCR technique. These cells transplanted into rats with spinal cord injury. Immunohistochemistry and immunofluorescence with subsequent quantification revealed that the expression of the axon...

Due to the morbidity and resulting lifestyle changes of Spinal Cord Injuries (SCI), there has been an extensive need to evaluate potential treatments. Mesenchymal cells hold the capacity to address both the primary and secondary mechanisms of SCI. Human Umbilical Cord stem cells (hUC), in particular, show promise due to their rapid proliferation, immunological properties, and pluripotent capacity. These hUC-MSC can be isolated from the umbilical Cord Blood (hCB) and Wharton's jelly, a viscous gel that maintains the umbilical cord's integrity. While Wharton's jelly-derived hUC-MSCs appear to have a greater capability for the treatment of SCI due to their increased proliferation, hCB-MSC additionally has long-term therapeutic potential in clinical trials.

The renal proximal tubule is a main target for drug-induced toxicity. The prediction of proximal tubular toxicity during drug development remains difficult. Any in vitro methods based on induced pluripotent stem cell-derived renal cells had not been developed, so far. Here, we developed a rapid 1-step protocol for the differentiation of human induced pluripotent stem cells (hiPSC) into proximal tubular-like cells. These proximal tubular-like cells had a purity of >90% after 8 days of differentiation and could be directly applied for compound screening. The nephrotoxicity prediction performance of the cells was determined by evaluating their responses to 30 compounds. The results were automatically determined using a machine learning algorithm called random forest. In this way, proximal tubular toxicity in humans could be predicted with 99.8% training accuracy and 87.0% test accuracy. Further, we studied the underlying mechanisms of injury and drug-induced cellular pathways in the...

Cellular therapy aims to replace damaged resident cells by restoring cellular and molecular environments suitable for tissue repair and regeneration. Among several candidates, mesenchymal stem/stromal cells (MSCs) represent a critical component of stromal niches known to be involved in tissue homeostasis. In vitro, MSCs appear as fibroblast-like plastic adherent cells regardless of the tissue source. The therapeutic value of MSCs is being explored in several conditions, including immunological, inflammatory and degenerative diseases, as well as cancer. An improved understanding of their origin and function would facilitate their clinical use. The stemness of MSCs is still debated and requires further study. Several terms have been used to designate MSCs, although consensual nomenclature has yet to be determined. The presence of distinct markers may facilitate the identification and isolation of specific subpopulations of MSCs. Regarding their therapeutic properties, the mechanisms u...

An increase in the accuracy of monitoring of glucose concentration indicators and an increase in the running time of glucose sensors are promising directions in the field of diabetology. One of the ways to extend the lifetime of a sensor is its complete implantation excluding direct communication with the skin surface. For effective long-term functioning in the patient’s body, the surface of an implantable sensor should be highly biocompatibile: it should not induce allergic and inflammatory reactions as well as the demarcation reaction (formation of a dense connective tissue capsule). Earlier, a group of authors developed a glucose-permeable membrane and a biocompatible coating comprising a complex of nadroparin with transesterified polyethylene glycol and γ-aminopropyl triethoxysilane, which formed a protein repellent hydrogel on the membrane surface. Aims. To evaluate the biocompatibility of the experimental coated membrane implanted into laboratory animals. Methods. The experime...

Rheumatoid arthritis is a chronic inflammatory and systemic autoimmune disease characterized by joint pain, swelling and stiffness. Inflammatory mediators such as pro-inflammatory cytokines, IL-6, COX-2, TNFalpha, etc. attack joints upon activation and generate reactive oxygen/nitrogen species, causing oxidative stress. High risk of opportunistic infections has also been reported in patients associated with the use of TNF-α inhibitors, corticosteroids and methotrexate drugs. Use of herbal medicine is becoming popular due to their negligible toxicity and rare side effects. The present study emphasizes the use of a bioprospection model which includes random search, priority indexing and rationale based selection of natural plant products targeting key descriptors of the disease. The identified plants could be used as nutraceuticals to ameliorate the vulnerable condition in inflammatory disorder(s). Further in vitro and in vivo analysis is also warranted, so as to validate the findings...

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X211035625 for Preclinical <i>in vivo</i> longitudinal assessment of KG207-M as a disease-modifying Alzheimer's disease therapeutic by Min Su Kang, Monica Shin, Julie Ottoy, Arturo Aliaga Aliaga, Sulantha Mathotaarachchi, Kely Quispialaya, Tharick A Pascoal, D Louis Collins, M. Mallar Chakravarty, Axel Mathieu, Åsa Sandelius, Kaj Blennow, Henrik Zetterberg, Gassan Massarweh, Jean-Paul Soucy, A Claudio Cuello, Serge Gauthier, Michael Waterston, Nathan Yoganathan, Etienne Lessard, Arsalan Haqqani, Kerry Rennie, Danica Stanimirovic, Balu Chakravarthy and Pedro Rosa-Neto in Journal of Cerebral Blood Flow & Metabolism

Discrepancies in preclinical studies of aspirin (ASA) antiplatelet activity in mouse models of bleeding and arterial thrombosis led us to evaluate commonly reported methods in order to propose a procedure for reliably measuring the effects of single dose ASA on mouse hemostasis. FVB and C57Bl6 mice received 100 mg/kg of ASA or vehicle orally 30 min or 3 h prior to investigate either hemostasis using the tail bleeding assay or carotid thrombosis induced by FeCl 3 , or to blood sampling for isolated platelet aggregation and TXB 2 generation. Expected inhibition of COX1 by ASA was ascertained by a strong decrease in TXB 2 production, and its effect on platelet function and hemostasis, by decreased collagen--induced aggregation and increased bleeding time, respectively. Strikingly, we determined that anti--hemostatic effects of ASA were more predictable 30 min after administration than 3 h later. Conversely, ASA did not alter time to arterial occlusion of the carotid upon FeCl 3 --induced thrombosis, suggesting ASA not to be used as reference inhibitor drug in this model of arterial thrombosis.

Paraplegia is the damage or loss of function in motor and/or sensory abilities. This insult can be observed in the thoracic, lumbar, or sacral parts of spinal column. Besides, paraplegia may be occurring because of any injuries or diseases of the lower segments or peripheral nerves or by cerebral palsy (CP). This damage can be seen as a result of a tumor or blood clot on the spinal cord. By now, there is not any curative treatment for paraplegia. Using mesenchymal stem cells (MSCs) in the treatment of spinal cord injury is a promising tested strategy because of their simplicity of isolation/preservation and their properties. Several preclinical studies in this field can be found; however, MSCs showed weak and conflicting outcomes in trials. In this chapter book, we will discuss about the therapeutic role of these cells in the treatment of paraplegia, with emphasis on their characterization, relevance, boundaries, and prospect views.