Pneumostem (human umbilical cord blood-derived mesenchymal stem cells) / Medipost, Samsung Medical Center - LARVOL DELTA

Efficacy and Safety of Pneumostem® for IVH in Premature Infants (Phase 2a) (clinicaltrials.gov) - P2 | N=22 | Active, not recruiting | Sponsor: Samsung Medical Center | Unknown status ➔ Active, not recruiting | Phase classification: P2a ➔ P2 | Trial completion date: Dec 2021 ➔ Dec 2025 | Trial primary completion date: Dec 2020 ➔ Dec 2025

Enrollment closed • Phase classification • Trial completion date • Trial primary completion date • Transplantation

Follow-up Study of Safety and Efficacy in Subjects Who Completed PNEUMOSTEM® Phase II (MP-CR-012) Clinical Trial (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Medipost Co Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

PNEUMOSTEM for the Prevention and Treatment of Severe BPD in Premature Infants (clinicaltrials.gov) - P2 | N=60 | Completed | Sponsor: Medipost Co Ltd. | Recruiting ➔ Completed | Trial completion date: Mar 2024 ➔ Oct 2024

Trial completion • Trial completion date • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

Mesenchymal Stromal Cells Primed by Toll-like Receptors 3 and 4 Enhanced Anti-Inflammatory Effects against LPS-Induced Macrophages via Extracellular Vesicles. (PubMed, Int J Mol Sci) - "We further confirmed that TLR-primed MSC-derived EVs can exert anti-inflammatory and immunosuppressive effects alone comparable to MSC treatment. We hereby suggest that in the LPS-induced macrophage in vitro model, EVs derived from both TLR3 and TLR4-primed MSCs can be a therapeutic candidate by promoting the M2 phenotype."

Journal • Stroma • Acute Lung Injury • Inflammation • Pneumonia • Respiratory Diseases • TLR3 • TLR4

PNEUMOSTEM for the Prevention and Treatment of Severe BPD in Premature Infants (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Medipost Co Ltd. | Unknown status ➔ Recruiting | Trial completion date: Jul 2021 ➔ Mar 2024 | Trial primary completion date: Jun 2021 ➔ Dec 2023

Enrollment open • Trial completion date • Trial primary completion date • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

Extracellular Vesicles Derived from Three-Dimensional-Cultured Human Umbilical Cord Blood Mesenchymal Stem Cells Prevent Inflammation and Dedifferentiation in Pancreatic Islets. (PubMed, Stem Cells Int) - "The greater suppression of IL-1β, NLRP3 inflammasome, caspase-1, and Oct4 and induction of Pdx1 and FoxO1 were found in islets cultured with the EVs derived from 3D hUCB-MSCs. In conclusion, EVs derived from 3D hUCB-MSCs optimized for M2 polarization attenuated nonspecific inflammation and preserved β-cell identity of pancreatic islets."

Journal • Immunology • Inflammation • FOXO1 • IL1B • NLRP3 • PDX1 • POU5F1

Headway and the remaining hurdles of mesenchymal stem cells therapy for bronchopulmonary dysplasia. (PubMed, Clin Respir J) - "With BPD existing as a constant threat and there being no permanent solutions, the idea of regenerative medicine such as MSC may prove to be a breakthrough strategy when it comes to treating BPD. The success in clinical trials led to the formulation of prospective MSC-derived products such as PNEUMOSTEM®, and there is the possibility of a stem cell medication and permanent treatment for BPD in the near future."

Journal • Review • Bronchopulmonary Dysplasia • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

HLA-A2 Promotes the Therapeutic Effect of Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Hyperoxic Lung Injury. (PubMed, Bioengineering (Basel)) - "Moreover, HLA-A2 silencing in MSCs significantly decreased their therapeutic effects in a rat model of hyperoxic lung damage. The present study provides novel insights into the quality control of donor-derived MSCs for the treatment of inflammatory conditions and diseases."

Journal • Immunology • Inflammation • Respiratory Diseases

Intracerebroventricular Administration of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Induces Transient Inflammation in a Transgenic Mouse Model and Patients with Alzheimer's Disease. (PubMed, Biomedicines) - "Interestingly, we discovered that pro-inflammatory cytokine levels were higher in the hUCB-MSC group. Taken together, our data suggest that the cause of transient inflammatory response observed from both the clinical trial and mouse study was due to the transplanted hUCB-MSCs."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Immunology • Infectious Disease • Inflammation • Oncology • Transplantation • CRP • IL1B • IL6 • TNFA

CD26 Inhibition Potentiates the Therapeutic Effects of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells by Delaying Cellular Senescence. (PubMed, Front Cell Dev Biol) - "CD26-negative MSCs also showed superior therapeutic efficacy in mouse lung emphysema model. Our present results collectively suggest CD26 is a potential novel target for the rejuvenation of senescent MSCs for their use in manufacturing MSC-based applications."

Journal • Inflammation • Pulmonary Disease • Pulmonary Emphysema • Respiratory Diseases • DPP4

Outcomes of human umbilical cord blood-derived mesenchymal stem cells in enhancing tendon-graft healing in anterior cruciate ligament reconstruction: an exploratory study. (PubMed, Knee Surg Relat Res) - "Allogeneic hUCB-MSCs were used safely for ACL reconstruction without treatment-related adverse event in a 2-year follow-up. However, our study did not suggest any evidence to show clinical advantage such as the prevention of tunnel enlargement postoperatively and a decrease in knee laxity or improvement of clinical outcomes."

Journal • Orthopedics

Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer's disease dementia: a phase I clinical trial. (PubMed, Alzheimers Res Ther) - P1/2 | "Three repeated administrations of hUCB-MSCs into the lateral ventricle via an Ommaya reservoir were feasible, relatively and sufficiently safe, and well-tolerated. Currently, we are undergoing an extended follow-up study for those who participated in a phase IIa trial where upon completion, we hope to gain a deeper understanding of the clinical efficacy of MSC AD therapy."

Clinical • Journal • P1 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Pain • Transplantation

Positively Correlated CD47 Activation and Autophagy in Umbilical Cord Blood-Derived Mesenchymal Stem Cells during Senescence. (PubMed, Stem Cells Int) - "Additionally, autophagy-related markers, ATG5, ATG12, Beclin1, and LC3B, revealed significant downregulation with CD47 siRNA transfection. Furthermore, autophagy flux following treatment with an autophagy inducer, rapamycin, has shown that CD47 is a key player in autophagy and senescence to maintain and regulate the growth of MSCs, suggesting that CD47 may be a critical key marker for the selection of effective stem cells in cell therapy."

Journal • ATG5 • CD47

Stem cell restores thalamocortical plasticity to rescue cognitive deficit in neonatal intraventricular hemorrhage. (PubMed, Exp Neurol) - "This is induced by the suppression of Hebbian plasticity via an increase in tumor necrosis factor-α expression during the critical period, which can be effectively reversed by the transplantation of MSCs. Furthermore, we showed that MSC transplantation successfully rescued IVH-induced learning deficits in the sensory-guided decision-making in correlation with TC FFI in the layer 4 barrel cortex."

Journal • CNS Disorders • Cognitive Disorders • Developmental Disorders • Hematological Disorders • Transplantation • TNFA

Follow-up Safety and Efficacy Evaluation on Subjects Who Completed PNEUMOSTEM® Phase-II Clinical Trial (clinicaltrials.gov) - P=N/A; N=62; Completed; Sponsor: Medipost Co Ltd.; Recruiting ➔ Completed; Phase classification: P2 ➔ PN/A

Clinical • Phase classification • Trial completion • Bronchopulmonary Dysplasia

Safety and Efficacy of PNEUMOSTEM® in Premature Infants at High Risk for Bronchopulmonary Dysplasia (BPD) - a US Study (clinicaltrials.gov) - P1/2; N=12; Completed; Sponsor: Medipost America Inc.; Active, not recruiting ➔ Completed

Trial completion • Biosimilar • Rare Diseases • Retinopathy of Prematurity

Follow-up Study of Safety and Efficacy in Subjects Who Completed PNEUMOSTEM® Phase II (MP-CR-012) Clinical Trial (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Medipost Co Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Human umbilical cord blood derived mesenchymal stem cells reduces phosphorylation and aggregation of tau in Alzheimer’s disease model (AAIC 2019) - "hUCB-MSCs diminish the phosphorylation and aggregation of tau through regulation of hUCB-MSCs, thus elucidating a therapeutic mechanism for AD."

Follow-up Study of Safety and Efficacy in Subjects Who Completed PNEUMOSTEM® Phase II (MP-CR-012) Clinical Trial (clinicaltrials.gov) - P2; N=60; Not yet recruiting; Sponsor: Medipost Co Ltd.

Clinical • New P2 trial

Follow-Up Study of Safety and Efficacy of Pneumostem® in Premature Infants With Bronchopulmonary Dysplasia (clinicaltrials.gov) - P=N/A; N=9; Active, not recruiting; Sponsor: Samsung Medical Center; Phase classification: P1 ➔ P=N/A; Trial completion date: Sep 2017 ➔ Sep 2026; Trial primary completion date: Sep 2017 ➔ Sep 2025

Clinical • Phase classification • Trial completion date • Trial primary completion date

Efficacy and Safety of Pneumostem® for IVH in Premature Infants (Phase 2a) (clinicaltrials.gov) - P2a; N=22; Recruiting; Sponsor: Samsung Medical Center; Trial completion date: Dec 2019 ➔ Dec 2021; Trial primary completion date: Aug 2019 ➔ Dec 2020

Clinical • Trial completion date • Trial primary completion date

Follow-Up Study of Safety of Pneumostem® in Premature Infants With Intraventricular Hemorrhage (clinicaltrials.gov) - P=N/A; N=9; Active, not recruiting; Sponsor: Samsung Medical Center; Enrolling by invitation ➔ Active, not recruiting; Trial primary completion date: Dec 2018 ➔ Dec 2022

Clinical • Enrollment closed • Trial primary completion date

PNEUMOSTEM for the Prevention and Treatment of Severe BPD in Premature Infants (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Medipost Co Ltd.; Not yet recruiting ➔ Recruiting; Initiation date: Jan 2019 ➔ Aug 2018

Clinical • Enrollment open • Trial initiation date