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-

Action-

Mechanism

Stem cell replacements

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesOther Diseases+ [1]

Active Indication

AggressionAgitation in DementiaAlzheimer Disease+ [5]

Inactive Indication

Acute Ischemic StrokeCrohn DiseaseDepressive Disorder, Treatment-Resistant

Originator Organization

University of Miami

Active Organization

University of Miami

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Frailty is a medical syndrome associated with advancing age characterized by reduced functional reserve, strength, endurance, and susceptibility to infection associated with high morbidity, hospitalization, and death. Nonspecific interventions to improve the healthspan of affected patients include physical therapy, exercise, improved nutrition, etc. Among the hallmarks of aging, depletion of stem cells with resultant compromise of regeneration and repair of tissues informs a rational stem cell-based replacement strategy. This hypothesis has been evaluated in a randomized, double-blind, placebo-controlled clinical trial utilizing human allogeneic mesenchymal stem cells (allo-hMSCs), a facile, scalable stem cell replacement therapy. Intravenous infusion of 100 or 200 million allo-hMSCs was deemed safe in aged frail individuals. However, modest improvement outcomes were limited to the lower dose, a finding that remains difficult to explain. Future studies are definitely warranted given the magnitude of this increasingly important medical syndrome.

01 Dec 2017·Stem cell research & therapy

Systemic administration of mesenchymal stem cells combined with parathyroid hormone therapy synergistically regenerates multiple rib fractures

Article

Author: Gazit, Zulma ; De Mel, Sandra ; Tawackoli, Wafa ; Yalon, Eran ; Pelled, Gadi ; Sheyn, Dmitriy ; Gazit, Dan ; Bez, Maxim ; Ley, Eric J ; Ben-David, Shiran ; Yaya, Alin ; Cohn Yakubovich, Doron ; Schary, Yeshai ; Amira, May ; Sirhan, Afeef ; Da, Xiaoyu

BACKGROUND:

A devastating condition that leads to trauma-related morbidity, multiple rib fractures, remain a serious unmet clinical need. Systemic administration of mesenchymal stem cells (MSCs) has been shown to regenerate various tissues. We hypothesized that parathyroid hormone (PTH) therapy would enhance MSC homing and differentiation, ultimately leading to bone formation that would bridge rib fractures.

METHODS:

The combination of human MSCs (hMSCs) and a clinically relevant PTH dose was studied using immunosuppressed rats. Segmental defects were created in animals' fifth and sixth ribs. The rats were divided into four groups: a negative control group, in which animals received vehicle alone; the PTH-only group, in which animals received daily subcutaneous injections of 4 μg/kg teriparatide, a pharmaceutical derivative of PTH; the hMSC-only group, in which each animal received five injections of 2 × 10⁶ hMSCs; and the hMSC + PTH group, in which animals received both treatments. Longitudinal in vivo monitoring of bone formation was performed biweekly using micro-computed tomography (μCT), followed by histological analysis.

RESULTS:

Fluorescently-dyed hMSCs were counted using confocal microscopy imaging of histological samples harvested 8 weeks after surgery. PTH significantly augmented the number of hMSCs that homed to the fracture site. Immunofluorescence of osteogenic markers, osteocalcin and bone sialoprotein, showed that PTH induced cell differentiation in both exogenously administered cells and resident cells. μCT scans revealed a significant increase in bone volume only in the hMSC + PTH group, beginning by the 4^th week after surgery. Eight weeks after surgery, 35% of ribs in the hMSC + PTH group had complete bone bridging, whereas there was complete bridging in only 6.25% of ribs (one rib) in the PTH-only group and in none of the ribs in the other groups. Based on the μCT scans, biomechanical analysis using the micro-finite element method demonstrated that the healed ribs were stiffer than intact ribs in torsion, compression, and bending simulations, as expected when examining bone callus composed of woven bone.

CONCLUSIONS:

Administration of both hMSCs and PTH worked synergistically in rib fracture healing, suggesting this approach may pave the way to treat multiple rib fractures as well as additional fractures in various anatomical sites.

12 Oct 2017·The journals of gerontology. Series A, Biological sciences and medical sciencesQ1 · MEDICINE

Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Q1 · MEDICINE

Article

Author: Medina, Audrey ; Mendizabal, Adam ; Goldstein, Bradley J ; Heldman, Alan W ; Natsumeda, Makoto ; DiFede, Darcy L ; Florea, Victoria ; Levis-Dusseau, Silvina ; Pujol, Marietsy V ; Goldschmidt-Clermont, Pascal J ; El-Khorazaty, Jill ; Schulman, Ivonne Hernandez ; Vidro-Casiano, Mayra ; Saltzman, Russell ; Landin, Ana Marie ; Anderson, Erica ; Green, Geoff ; Valasaki, Krystalenia ; Golpanian, Samuel ; Mushtaq, Muzammil ; Byrnes, John J ; Oliva, Anthony A ; Premer, Courtney ; Tompkins, Bryon A ; Hare, Joshua M ; Delgado, Cindy ; Lowery, Maureen ; Miki, Roberto ; Da Fonseca, Moisaniel ; Khan, Aisha

BACKGROUND:

Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal stem cells (allo-hMSCs) exert immunomodulatory effects and promote tissue repair.

METHODS:

This is a randomized, double-blinded, dose-finding study of intravenous allo-hMSCs (100 or 200-million [M]) vs placebo delivered to patients (n = 30, mean age 75.5 ± 7.3) with frailty. The primary endpoint was incidence of treatment-emergent serious adverse events (TE-SAEs) at 1-month postinfusion. Secondary endpoints included physical performance, patient-reported outcomes, and immune markers of frailty measured at 6 months postinfusion.

RESULTS:

No therapy-related TE-SAEs occurred at 1 month. Physical performance improved preferentially in the 100M-group; immunologic improvement occurred in both the 100M- and 200M-groups. The 6-minute walk test, short physical performance exam, and forced expiratory volume in 1 second improved in the 100M-group (p = .01), not in the 200M- or placebo groups. The female sexual quality of life questionnaire improved in the 100M-group (p = .03). Serum TNF-α levels decreased in the 100M-group (p = .03). B cell intracellular TNF-α improved in both the 100M- (p < .0001) and 200M-groups (p = .002) as well as between groups compared to placebo (p = .003 and p = .039, respectively). Early and late activated T-cells were also reduced by MSC therapy.

CONCLUSION:

Intravenous allo-hMSCs were safe in individuals with aging frailty. Treated groups had remarkable improvements in physical performance measures and inflammatory biomarkers, both of which characterize the frailty syndrome. Given the excellent safety and efficacy profiles demonstrated in this study, larger clinical trials are warranted to establish the efficacy of hMSCs in this multisystem disorder.

CLINICAL TRIAL REGISTRATION:

www.clinicaltrials.gov: CRATUS (#NCT02065245).

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
Aggression	Phase 2	United States	University of Miami	01 May 2025
Agitation in Dementia	Phase 2	United States	University of Miami	01 May 2025
Alzheimer Disease	Phase 2	United States	University of Miami	01 May 2025
Diabetes Mellitus, Noninsulin-Dependent, 2	Phase 2	United States	University of Miami	16 Aug 2021
Endothelial dysfunction	Phase 2	United States	University of Miami	16 Aug 2021
Myocardial Ischemia	Phase 2	United States	University of Miami	16 Aug 2021
Cardiomyopathy, Dilated	Phase 2	United States	University of Miami	07 May 2021
Non-ischemic Cardiomyopathy	Phase 2	United States	University of Miami	07 May 2021
Crohn Disease	Phase 1	United States	University of Miami	01 Dec 2019
Depressive Disorder, Treatment-Resistant	Phase 1	United States	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)	fbhuadwfrc = ilgweepocf nbsneewllv (gygmpgxkjn, kwkukufxaq - rdecrzuijk) View more	-	11 May 2022
				100 million Allogeneic Mesenchymal Human Stem Cells (Pilot Phase 100 Million hMSCs)	fbhuadwfrc = lcrhhirhvk nbsneewllv (gygmpgxkjn, uccuwifhai - gszzykxart) View more
NCT02065245 (CRATUS, CTgov)	Phase 1/2	Frailty Syndrome	65	Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) (Pilot Phase - Group 1)	wdlizupvuv = cmxclommjn fdxxodpnru (zkqdkweczg, ezjkdqqlbe - fjgmbmpwox) View more	-	27 Apr 2021
				Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) (Pilot Phase - Group 2)	wdlizupvuv = fwyawdhxoi fdxxodpnru (zkqdkweczg, vovqgyocck - peodsjuuuy) View more
NCT02013674 (Trident, CTgov)	Phase 2	Ventricular Dysfunction, Left \| Myocardial Infarction	30	Allogeneic hMSCs (Group 1: 20 Million Allogeneic hMSCs)	taptfnjqdd = wcmkzbsjbe pnwxyloymf (knpfeqkxoy, wbawndsjlq - zjkperjvhr) View more	-	05 Feb 2020
				Allogeneic hMSCs (Group 2: 100 Million Allogeneic hMSCs)	taptfnjqdd = weaihgeewz pnwxyloymf (knpfeqkxoy, uspycgnxsh - tiecjrpmlk) View more
NCT01392625 (PoseidonDCM, CTgov)	Phase 1/2	Cardiomyopathy, Dilated	37	Autologous hMSCs (Autologous hMSCs)	dxaxxafwgp = buupxiyerb iouwejztna (kwsbbhastj, riogehlocy - njkidtpfay) View more	-	15 Feb 2018
				Allogeneic hMSCs (Allogeneic hMSCs)	dxaxxafwgp = pdufhjpzho iouwejztna (kwsbbhastj, klxexbpwpp - xtppfawliq) View more