Safety study of autologous adult bone marrow derived mesenchymal stromal cells in idiopathic pulmonary fibrosis - Pilot data

2017 ◽  
Vol 4 (1-4) ◽  
pp. 15-22
Author(s):  
Lakshmi Kiran Chelluri ◽  
Upasna Upadhyay ◽  
Ravindra Nallagonda ◽  
Sudhir Prasad ◽  
Mohammad Samiuddin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Safety Study ◽  
Pilot Data ◽  
Adult Bone Marrow ◽  
Adult Bone

scholarly journals Endobronchial autologous bone marrow-mesenchymal stromal cells in idiopathic pulmonary fibrosis (phase I)

2021 ◽  
pp. 00773-2020
Author(s):  
Arantza Campo ◽  
José María González-Ruiz ◽  
Enrique Andreu ◽  
Ana B. Alcaide ◽  
María M. Ocón ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Adverse Events ◽  
Phase I ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Second Phase ◽  
Endobronchial Administration

RationaleIdiopathic pulmonary fibrosis (IPF) has a dismal prognosis. Mesenchymal stromal cells have shown benefit in other inflammatory diseases.ObjectivesEvaluate the safety and feasibility of endobronchial administration of bone marrow autologous MSCs (BM-MSC) in patients with mild-to-moderate IPF.MethodsA phase-I multicenter clinical Trial (ClinicalTrials.gov:NCT01919827) with a single endobronchial administration of autologous adult BM-MSC in patients diagnosed with mild-to-moderate IPF. In a first escalating-dose phase, 3 patients will be included sequentially in 3 dose cohorts (10×10^6, 50×10^6, and 100×10^6 cells). In a second phase, 9 patients will receive the highest tolerated dose. Follow-up with PFT, 6MWT, and SGRQ were done at 1, 2, 3, 6, and 12 months, and with a computed tomography at 3, 6, and 12 months.FindingsTwenty-one bone marrow samples were obtained from 17 patients. Three patients were excluded for treatment due to chromosome aberrations detected in MSCs after culture, and one patient died before treatment. Finally, 13 patients received the BM-MSCs infusion. No treatment related severe adverse events were observed during follow-up. Compared to baseline, the mean FVC showed an initial decline of 8.1% at three months. The number of patients without functional progression was 6 (46%) at 3 months and 3 (23%) at 12 months.ConclusionsThe endobronchial infusion of BM-MSCs did not cause immediate serious adverse events in IPF patients, but a relevant proportion of patients suffered clinical and/or functional progression. Genomic instability of BM-MSCs during culture found in three patients may be troublesome for the use of autologous MSCs in IPF patients.

scholarly journals Leptin-Receptor-Expressing Mesenchymal Stromal Cells Represent the Main Source of Bone Formed by Adult Bone Marrow

2014 ◽  
Vol 15 (2) ◽  
pp. 154-168 ◽  
Author(s):  
Bo O. Zhou ◽  
Rui Yue ◽  
Malea M. Murphy ◽  
James G. Peyer ◽  
Sean J. Morrison
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Leptin Receptor ◽  
Adult Bone Marrow ◽  
Adult Bone

scholarly journals Leptin Receptor Promotes Adipogenesis and Reduces Osteogenesis by Regulating Mesenchymal Stromal Cells in Adult Bone Marrow

2016 ◽  
Vol 18 (6) ◽  
pp. 782-796 ◽  
Author(s):  
Rui Yue ◽  
Bo O. Zhou ◽  
Issei S. Shimada ◽  
Zhiyu Zhao ◽  
Sean J. Morrison
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Leptin Receptor ◽  
Adult Bone Marrow ◽  
Adult Bone

scholarly journals Human bone marrow-derived mesenchymal stromal cells cultured in serum-free media demonstrate enhanced antifibrotic abilities via prolonged survival and robust regulatory T cell induction in murine bleomycin-induced pulmonary fibrosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shun Takao ◽  
Taku Nakashima ◽  
Takeshi Masuda ◽  
Masashi Namba ◽  
Shinjiro Sakamoto ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Pulmonary Fibrosis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Pulmonary Inflammation ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Distributed Data ◽  
Serum Free ◽  
Free Media

Abstract Background Mesenchymal stromal cells (MSCs) are a potential therapeutic tool for pulmonary fibrosis. However, ex vivo MSC expansion using serum poses risks of harmful immune responses or unknown pathogen infections in the recipients. Therefore, MSCs cultured in serum-free media (SF-MSCs) are ideal for clinical settings; however, their efficacy in pulmonary fibrosis is unknown. Here, we investigated the effects of SF-MSCs on bleomycin-induced pulmonary inflammation and fibrosis compared to those of MSCs cultured in serum-containing media (S-MSCs). Methods SF-MSCs and S-MSCs were characterized in vitro using RNA sequence analysis. The in vivo kinetics and efficacy of SF-MSC therapy were investigated using a murine model of bleomycin-induced pulmonary fibrosis. For normally distributed data, Student’s t test and one-way repeated measures analysis of variance followed by post hoc Tukey’s test were used for comparison between two groups and multiple groups, respectively. For non-normally distributed data, Kruskal–Wallis and Mann–Whitney U tests were used for comparison between groups, using e Bonferroni’s correction for multiple comparisons. All tests were two-sided, and P < 0.05 was considered statistically significant. Results Serum-free media promoted human bone marrow-derived MSC expansion and improved lung engraftment of intravenously administered MSCs in recipient mice. SF-MSCs inhibited the reduction in serum transforming growth factor-β1 and the increase of interleukin-6 in both the serum and the bronchoalveolar lavage fluid during bleomycin-induced pulmonary fibrosis. SF-MSC administration increased the numbers of regulatory T cells (Tregs) in the blood and lungs more strongly than in S-MSC administration. Furthermore, SF-MSCs demonstrated enhanced antifibrotic effects on bleomycin-induced pulmonary fibrosis, which were diminished by antibody-mediated Treg depletion. Conclusions SF-MSCs significantly suppressed BLM-induced pulmonary inflammation and fibrosis through enhanced induction of Tregs into the lungs and corrected the dysregulated cytokine balance. Therefore, SF-MSCs could be a useful tool for preventing pulmonary fibrosis progression without the demerits of serum use.

scholarly journals Thrombopoietin Is Synthesized by Bone Marrow Stromal Cells

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3444-3455 ◽  
Author(s):  
Anastasia Guerriero ◽  
Lydia Worford ◽  
H. Kent Holland ◽  
Gui-Rong Guo ◽  
Kevin Sheehan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Cell Sorting ◽  
Bone Marrow Cells ◽  
Adult Bone Marrow ◽  
Hla Dr ◽  
Adult Bone ◽  
Marrow Cells

Abstract We have previously characterized stromal progenitor cells contained in fetal bone marrow by fluorescence-activated cell sorting (FACS) using the differential expression of CD34, CD38, and HLA-DR, and found that a small number were contained within the CD34+ cell fraction. In the present study, the frequency of stromal progenitors in both the CD34+ and CD34− subpopulations from samples of fetal and adult bone marrow was approximately one in 5,000 of the mononuclear cell fraction. Using multiparameter single-cell sorting, one in 20 fetal bone marrow cells with the CD34+, CD38−, HLA-DR−, CDw90+ phenotype were clonogenic stromal progenitors, whereas greater than one in five single cells with the CD34−, CD38−, HLA-DR−, CDw90+ phenotype formed stromal cultures. We found that cultures initiated by hematopoietic and stromal progenitors contained within the CD34+ fraction of bone marrow cells formed mixed hematopoietic/stromal cell cultures that maintained the viability of the hematopoietic progenitor cells for 3 weeks in the absence of added hematopoietic cytokines. We characterized some of the hematopoietic cytokines synthesized by stromal cultures derived from either CD34+ or CD34− bone marrow cells using reverse transcriptase–polymerase chain reaction (RT-PCR) amplification of interleukin-3 (IL-3), stem cell factor (SCF), CD34, Flt3/Flk2 ligand (FL), and thrombopoietin (TPO) mRNA sequences. We found ubiquitous expression of TPO mRNA in greater than 90% of stromal cultures initiated by either CD34+ or CD34− cells, and variable expression of SCF, FL, and CD34 mRNA. In particular, SCF and CD34 mRNA were detected only in stromal cultures initiated by CD34+ bone marrow cells, although the differences between CD34+ and CD34− stromal cells were not statistically significant. IL-3 mRNA was not found in any stromal cultures. An enzyme-linked immunosorbent assay (ELISA) of soluble SCF and TPO present in culture supernatants demonstrated that biologically significant amounts of protein were secreted by some cultured stromal cells: eight of 16 samples of conditioned media from stromal cultures initiated by fetal and adult bone marrow contained more than 32 pg/mL SCF (in the linear range of the ELISA), with a median value of 32 pg/mL (range, 9 to 230), while 13 of 24 samples of conditioned media had more than 16 pg/mL TPO (in the linear range of the ELISA), with a median of 37 pg/mL (range, 16 to 106). Our data indicate that stromal cultures initiated by single bone marrow cells can make FL, SCF, and TPO. Local production of early-acting cytokines and TPO by stromal cells may be relevant to the regulation of hematopoietic stem cell self-renewal and megakaryocytopoiesis in the bone marrow microenvironment.

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