Delving into the Latest Updates on Allogeneic human mesenchymal stem cells(University of Miami) with Synapse

Overview

Basic Info

Drug Type

Mesenchymal stem cell therapy

Synonyms

Allo-hMSCs

Target-

Mechanism

Stem cell replacements

Therapeutic Areas

Other DiseasesNervous System DiseasesCardiovascular Diseases

Active Indication-

Inactive Indication

Acute Ischemic StrokeDepressive Disorder, Treatment-Resistant

Originator Organization

University of Miami

Active Organization-

Inactive Organization

University of Miami

Drug Highest PhaseDiscontinuedPhase 1

First Approval Date-

Regulation-

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AbstractObjectiveIncreasing magnesium intake might reduce the risk of cardiovascular disease (CVD). Whether potential effects on cortisol contribute to these beneficial effects on cardiovascular health remains unclear. We therefore studied effects of long‐term oral magnesium supplementation on glucocorticoid metabolism, specifically on the excretion of urinary cortisol, cortisone and their metabolites, as well as on the ratios reflecting enzymatic activity of 11β‐hydroxysteroid dehydrogenases (11β‐HSDs) and A‐ring reductases.DesignA post‐hoc analysis of a randomized trial with allocation to a magnesium supplement (350 mg/day) or a placebo for 24‐week.PatientsForty‐nine overweight men and women, aged between 45 and 70 years.MeasurementsCortisol, cortisone and their metabolites (tetrahydrocortisol [THF], allo‐tetrahydrocortisol [allo‐THF] and tetrahydrocortisone [THE]) were measured in 24‐h urine samples. Enzymatic activities of 11β‐HSD overall and of 11β‐HSD type 2 were estimated as the urinary (THF + allo‐THF [THFs])/THE and cortisol/cortisone ratios, respectively. A‐ring reductase activity was assessed by ratios of THF/allo‐THF, allo‐THF/cortisol, THF/cortisol and THE/cortisone.ResultsAfter 24‐week, urinary cortisol excretion was decreased in the magnesium group as compared with the placebo group (−32 nmol/24‐h, 95% CI: −59; −5 nmol/24‐h, p = .021). Ratios of THFs/THE and cortisol/cortisone were decreased following magnesium supplementation by 0.09 (95% CI: 0.02; 0.17, p = .018) and 0.10 (95% CI: 0.03; 0.17, p = .005), respectively. No effects were observed on A‐ring reductase activity.ConclusionsWe observed a beneficial effect of magnesium supplementation towards a lower 24‐h urinary cortisol excretion together with an increased activity of 11β‐HSD type 2. Our findings may provide another potential mechanism by which increased magnesium intake lowers CVD risk (ClinicalTrials.gov identifier: NCT02235805).

01 Jun 2020·TransplantationQ2 · MEDICINE

LPS-induced Airway-centered Inflammation Leading to BOS-like Airway Remodeling Distinct From RAS-like Fibrosis in Rat Lung Transplantation

Q2 · MEDICINE

Article

Author: Hamaji, Masatsugu ; Yoshizawa, Akihiko ; Aoyama, Akihiro ; Date, Hiroshi ; Saito, Masao ; Gochi, Fumiaki ; Sato, Masaaki ; Urushiyama, Hirokazu ; Chen-Yoshikawa, Toyofumi F ; Sonobe, Makoto ; Takahagi, Akihiro ; Miyamoto, Ei ; Terasaki, Yasuhiro

Background.Localization of inflammatory stimuli may direct lung allografts to different phenotypes of chronic dysfunction, such as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). We hypothesized that airway stimulation with lipopolysaccharide (LPS) in rats leads to airway-centered inflammation similar to human BOS.Methods.Rat left lung transplantation was conducted (donor: Brown Norway, recipient: Lewis). Allotransplant recipients received cyclosporine A (CsA) until postoperative day 56 with airway instillation of LPS (Allo-LPS, n = 8), phosphate buffered saline (Allo-PBS, n = 5) from days 35 to 46 (3 times a wk), or no further treatment (n = 4). Some allotransplant recipients received CsA until day 14 and were immunosuppression free after day 15 until day 56. Bronchial and pleural fibrosis were semiquantified; alveolar fibrosis was evaluated with a histological scale.Results.The Allo-LPS group had significantly increased International Society for Heart and Lung Transplantation rejection grades (grade A, P = 0.005; grade B, P = 0.004), bronchial obstructive proportion (0.34 ± 0.04% [Allo-LPS] versus 0.11 ± 0.04% [Allo-PBS], P = 0.006), and airway resistance (3.05 ± 1.78 cm H2O·s/mL [Allo-LPS] versus 0.83 ± 0.58 cm H2O·s/mL [Allo-PBS], P = 0.007) compared with other groups. Allotransplant recipients that underwent a short course of CsA developed RAS-like fibrosis involving the airways, alveoli, and pleura.Conclusions.Airway instillation of LPS in allografts under immunosuppression resulted in BOS-like airway-centered inflammation and fibrosis distinct from RAS-like diffuse fibrosis, which was induced by a shortened course of immunosuppression. We propose novel animal models for BOS and RAS after lung transplantation.

01 Nov 2019·CorneaQ3 · MEDICINE

In Vivo Confocal Microscopy Automated Morphometric Analysis of Corneal Subbasal Nerve Plexus in Patients With Dry Eye Treated With Different Sources of Homologous Serum Eye Drops

Q3 · MEDICINE

Article

Author: Pellegrini, Marco ; Moscardelli, Fabiana ; Giannaccare, Giuseppe ; Bernabei, Federico ; Versura, Piera ; Buzzi, Marina ; Campos, Emilio C

Purpose:To investigate the comparative effect of allogeneic peripheral blood serum (allo-PBS) and cord blood serum (CBS) eye drops on the status of the corneal subbasal nerve plexus in patients with dry eye disease by using an automated analysis system of in vivo confocal microscopy images.Methods:This prospective, randomized, double-blind study included 30 patients with severe dry eye disease assigned to receive allo-PBS (group 1) or CBS (group 2) eye drops 8 times a day for 30 days. The following in vivo confocal microscopy parameters were calculated with ACCMetrics before (visit 1 [V1]) and after treatment (visit 2 [V2]): corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length, corneal nerve total branch density, corneal nerve fiber area, corneal nerve fiber width, and corneal nerve fractal dimension (CNFrD).Results:In overall patients, the values of corneal nerve fiber density, corneal nerve fiber length, and CNFrD significantly increased, whereas the value of corneal nerve fiber width significantly decreased at V2 compared with V1 (respectively, 20.4 ± 7.9 vs. 17.4 ± 10.1 n/mm2; 13.5 ± 4.0 vs. 12.0 ± 5.1 mm/mm2; 1.466 ± 0.046 vs. 1.475 ± 0.033; and 0.022 ± 0.002 vs. 0.023 ± 0.002; all P < 0.05). In the subanalysis according to the treatment type, the increase of CNFrD value from V1 to V2 was higher in group 2 compared with group 1 (respectively, from 1.455 ± 0.041 to 1.471 ± 0.030 and from 1.479 ± 0.050 to 1.481 ± 0.035; P = 0.030).Conclusions:Overall, both treatments significantly improved corneal subbasal nerve plexus parameters, and in particular, nerve density, length, width, and fractal dimension. Treatment with CBS eye drops was associated with a higher increase of CNFrD compared with allo-PBS.

100 Deals associated with Allogeneic human mesenchymal stem cells(University of Miami)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Ischemic Stroke	Phase 1	US	University of Miami	31 Aug 2022
Depressive Disorder, Treatment-Resistant	Phase 1	US	University of Miami	31 Oct 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02886884 (ACESO, CTgov)	Phase 1/2	Diabetes Mellitus, Type 2 \| Endothelial dysfunction	16	20 million Allogeneic Mesenchymal Human Stem Cells (Pilot Phase 20 Million Allogeneic hMSCs)	clanrhctwp(dftxpwxflh) = vgqggxfcir uuykfljavr (ubqttasdyi, gcnlvfgkvl - qxjvjuespe) View more	-	11 May 2022
				100 million Allogeneic Mesenchymal Human Stem Cells (Pilot Phase 100 Million hMSCs)	clanrhctwp(dftxpwxflh) = njalfwnvyx uuykfljavr (ubqttasdyi, pwmbdsuzfu - umhbhncwzu) View more
NCT02013674 (Trident, CTgov)	Phase 2	Ventricular Dysfunction, Left \| Myocardial Infarction	30	Allogeneic hMSCs (Group 1: 20 Million Allogeneic hMSCs)	jlngfgulmn(oumfvgzdpm) = stmyuybbsv ugheojxhvl (hmhrfmqmsr, jebaqsaruu - idvzcujwxe) View more	-	05 Feb 2020
				Allogeneic hMSCs (Group 2: 100 Million Allogeneic hMSCs)	jlngfgulmn(oumfvgzdpm) = liqnwvnxjc ugheojxhvl (hmhrfmqmsr, htocbnqbrx - fmyczvhniv) View more
NCT01392625 (PoseidonDCM, CTgov)	Phase 1/2	Cardiomyopathy, Dilated	37	Autologous hMSCs (Autologous hMSCs)	(ctdvkqlvxd) = uvnzlrhynv idolltoqjv (xodbpvycbu, ftpygrvbhv - fkcsdnfrax) View more	-	15 Feb 2018
				Allogeneic hMSCs (Allogeneic hMSCs)	(ctdvkqlvxd) = youbwzlubw idolltoqjv (xodbpvycbu, rhecuohvny - uoflmkjtdp) View more
NCT00768066 (TAC-HFT, CTgov)	Phase 1/2	Ventricular Dysfunction, Left \| Myocardial Infarction \| Heart Failure	65	Autologous human mesenchymal cells (hMSCs) (200 Million Autologous Human Mesenchymal Stem Cells (hMSCs))	vfovorutdv(mzpjaujaat) = dwpjbmjurl zwrativwkp (olbxwsdaxm, iumtsrllxm - ptynibjppt) View more	-	14 Dec 2015
				Autologous human bone marrow cells (hBMCs) (200 Million Autologous Human Bone Marrow Cells (hBMCs))	vfovorutdv(mzpjaujaat) = ppzglhelgh zwrativwkp (olbxwsdaxm, ecobkurxee - kndnuujjkk) View more
NCT01087996 (CTgov)	Phase 1/2	Ventricular Dysfunction, Left \| Myocardial Infarction	31	Allo-hMSCs (Allo-hMSCs)	xznrluiohz(eniquysckd) = bgrzwvndgd damqwwkdyl (jkrkjxrcfr, wmcgnsvevw - schizuzrmq) View more	-	27 May 2015
				Auto-hMSCs (Auto-hMSCs)	xznrluiohz(eniquysckd) = wlywbrxvtq damqwwkdyl (jkrkjxrcfr, fjbtharjkb - jycmtlwhjv) View more