scholarly journals Transient Existence of Circulating Mesenchymal Stem Cells in the Deep Veins in Humans Following Long Bone Intramedullary Reaming

2020 ◽  
Vol 9 (4) ◽  
pp. 968 ◽  
Author(s):  
Sarah M Churchman ◽  
Elena A Jones ◽  
Tarek Roshdy ◽  
George Cox ◽  
Sally A Boxall ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Femoral Vein ◽  
Dermal Fibroblasts ◽  
Long Bone ◽  
Molecular Profile ◽  
Skeletal Trauma ◽  
Intramedullary Reaming ◽  
Healthy Donors

The biology of mesenchymal stem cells (MSCs) in humans is incompletely understood and a possible role of systemically circulating cells in health and autoimmune disease remains controversial. Physiological movement of bone marrow MSCs to sites of injury would support the rationale for intravenous administration for relocation to damaged organs. We hypothesized that biophysical skeletal trauma rather than molecular cues may explain reported MSC circulation phenomena. Deep-femoral vein (FV) and matched peripheral vein blood samples (PVBs) were collected from patients undergoing lower-limb orthopaedic procedures during surgery (tibia using conventional sequential reaming, n = 9, femur using reamer/irrigator/aspirator (RIA), n = 15). PVBs were also taken from early (n = 15) and established (n = 12) rheumatoid arthritis (RA) patients and healthy donors (n = 12). Colony-forming unit-fibroblasts (CFU-Fs) were found in 17/36 FVBs but only 7/74 PVBs (mostly from femoral RIA); highly proliferative clonogenic cells were not generated. Only one colony was found in control/RA samples (n = 28). The rare CFU-Fs’ MSC nature was confirmed by phenotypic: CD105+/CD73+/CD90+ and CD19−/CD31−/CD33−/CD34−/CD45−/CD61−, and molecular profiles with 39/80 genes (including osteo-, chondro-, adipo-genic and immaturity markers) similar across multiple MSC tissue controls, but not dermal fibroblasts. Analysis of FVB-MSCs suggested that their likely origin was bone marrow as only two differences were observed between FVB-MSCs and IC-BM-MSCs (ACVR2A, p = 0.032 and MSX1, p = 0.003). Stromal cells with the phenotype and molecular profile of MSCs were scarcely found in the circulation, supporting the hypothesis that their very rare presence is likely linked to biophysical micro-damage caused by skeletal trauma (here orthopaedic manipulation) rather than specific molecular cues to a circulatory pool of MSCs capable of repair of remote organs or tissues. These findings support the use of organ resident cells or MSCs placed in situ to repair tissues rather than systemic administration.

scholarly journals Senescent Mesenchymal Stem Cells Present at the Early Post Allogeneic Hematopoietic Stem Cell Transplantation Period Are Associated with an Increased Incidence of Acute Graft-Versus Host Disease and Increased Plasma Levels of Fas Ligand

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2116-2116
Author(s):  
Daniel Rivera ◽  
Lika Osugui ◽  
Sandra Muntion ◽  
Miguel Alcoceba ◽  
Concepcion Rodriguez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Board Of Directors ◽  
Fas Ligand ◽  
Ex Vivo ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Healthy Donors

Abstract Introduction Mesenchymal stem cells (MSC) are a key component of the hematopoietic niche. In the allogeneic hematopoietic stem cell transplantation (allo-HSCT) setting, the bone marrow stroma, and thus, their MSC remain of host origin. In a preliminary study we observed that, some patients at the early post allo-HSCT period, presented senescent bone marrow (BM) MSC, a finding that has not been previously described nor studied. The aims of our current study were: a) To multiparametrically characterize BM MSC at the early post allo-HSCT period (day +21). b) To confirm senescence of MSC and correlate with clinical and biological parameters (including biomarkers). c) To compare these cells with those from healthy donors. Methods We obtained BM samples on the day +21 post allo-HSCT from 136 patients. MSC were isolated, ex-vivo expanded and characterized, according to the criteria of the International Society for Cellular Therapy. We also obtained samples from peripheral blood at same day +21, for the study of biomarkers, which were analyzed by Luminex technique. The data were correlated with information from complete blood counts (CBC), and the morphological study of the bone marrow the same day. MSC from healthy donors were used as control. Results Patient baseline and transplant related characteristics are detailed in table 1. MSC were expanded ex-vivo showing normal growth, which were cryopreserved in passage 3 in the 33% (n=45/136) of the patients (Group-MSC-N). On the other hand, the remaining 67% (n=91/136), MSC showed premature signs of senescence, thus, not reaching to passage 1 (Group-MSC-S). Full BM chimerism on day+21 was seen in both groups (p=0.03). Concerning acute graft versus-host disease (aGVHD), in the Group-MSC-S, the incidence was 73% compared to 44% in the Group-MSC-N (p=0.001). The median time of the onset of aGVHD was 43 and 37 days respectively (p=0.04). The majority of cases presented with grades I-II in both groups. Plasma levels of biomarkers showed increased levels of Fas Ligand in the Group-MSC-S (p=0.009). There were no statistically significant differences regarding mortality nor relapse rates. Conclusions Bone marrow Mesenchymal stem cells may be severely damaged in some allo-HSCT recipients early after transplantation (day+21). This fact strongly correlates with the risk of development of acute GVHD. Disclosures Díez-Campelo: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

scholarly journals Bone Marrow Mesenchymal Stem Cells from Healthy Donors and Sporadic Amyotrophic Lateral Sclerosis Patients

2008 ◽  
Vol 17 (3) ◽  
pp. 255-266 ◽  
Author(s):  
Ivana Ferrero ◽  
Letizia Mazzini ◽  
Deborah Rustichelli ◽  
Monica Gunetti ◽  
Katia Mareschi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Amyotrophic Lateral Sclerosis ◽  
Mesenchymal Stem Cells ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Healthy Donors ◽  
Marrow Mesenchymal Stem Cells ◽  
Lateral Sclerosis

JAK2 Mutation Analysis and Function of Bone Marrow Mesenchymal Stem Cells in Myeloproliferative Neoplasms

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5179-5179
Author(s):  
Hong Tian ◽  
Yang Xu ◽  
Guanghua Chen ◽  
Man Qiao ◽  
Wu Depei
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Jak2v617f Mutation ◽  
Primary Study ◽  
Jak2 Mutation ◽  
Healthy Donors ◽  
Marrow Mesenchymal Stem Cells

Abstract Abstract 5179 Background: JAK2V617F and JAK2 exon12 mutations in haematopoietic cells were partially responsible for the pathogenesis of myeloproliferative neoplasms (MPN).But it was still unclear whether bone marrow mesenchymal stem cells (BMSCs), the significant component of hemopoiesis microenvironment, were participated in the pathogenesis of MPN. Objective: To study the physiopathology characteristics and analyze JAK2 mutation in BMSCs from MPN patients. Methods: By searched for the JAK2V617F mutation and exon 12 mutation in 135 MPN patients' blood /bone marrow samples, 20 patients with JAK2V617F mutation, 10 patients with JAK2 exon 12 mutation, 5 JAK2-mutation-negetive patients and 10 healthy donors were recruited. The phenotype, mesenchymal differentiation capacity, expression of hematopoietic and immune molecules and JAK2 mutation of isolated bone marrow BMSCs were detected. Results: BMSCs derived from the four groups were found to be similar in morphology, differentiation ability and expression of hematopoietic and immune molecules. Primary study indicated that the isolated BMSCs from patients groups were not able to harbor JAK2 mutation in spite of positive or negative JAK2 mutation in blood /bone marrow samples. Conclusion: BMSCs from MPN patients had similar biological characteristics to healthy donors, and BMSCs were not likely involved in pathogenesis of MPN. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Phenotypical and Functional Characterization of Mesenchymal Stem Cells Derived From Patients Affected by Schwachman-Diamond Syndrome

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1336-1336
Author(s):  
Valentina Andrée ◽  
Daniela Longoni ◽  
Silvia Bresolin ◽  
Geertruy Kronnie ◽  
Giovanni Cazzaniga ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Conflicts Of Interest ◽  
Functional Characterization ◽  
Genetic Defect ◽  
Dependent Manner ◽  
Molecular Features ◽  
Healthy Donors ◽  
A Genome

Abstract Abstract 1336 Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder with an incidence of 1 in 50.000 births. In 2001, the genetic defect of SDS was mapped to the centromeric region of chromosome 7 and in 2003 the defect was narrowed down to a single gene, which was named the Shwachman-Bodian-Diamond Syndrome (SBDS) gene. The mutations in the SBDS gene were identified in 90% of patients. Pancreatic exocrine insufficiency, bone marrow dysfunction with peripheral blood cytopenias, skeletal abnormalities, short stature and immune dysfunction characterize the disorder. Neutropenia plays a crucial role in the occurrence of recurrent and severe infectious complications representing one of the major causes of death in SDS patients. The aim of our study is to better comprehend the marrow dysfunction occurring in SDS patients, by analysing the functional properties of bone marrow (BM)-derived mesenchymal stem cells (MSCs). BM cells obtained from patients and healthy donors (HDs) were plated in sterile tissue culture flasks. At the third passage of the culture, cells were tested for the expression of specific surface markers, their ability to differentiate into mesengenic lineages, their capability to abrogate T cell proliferation and their ability to prevent neutrophil apoptosis. MSCs derived from SDS patients (SDS-MSCs) displayed typical fibroblastoid morphology; they were consistently devoid of contaminating hematopoietic cells, being negative for CD34, CD45, HLA-DR, CD11b, CD19, and CD14, but expressed common MSC markers including CD90, CD73, CD105 and HLA-ABC. Similarly to MSCs obtained from healthy donors (HD-MSCs), these cells were able to differentiate into adipocytes, osteoblasts and chondrocytes. In addition, SDS-MSCs drastically decreased the mitogen-induced lymphocyte proliferation, in a dose dependent manner. We also cultured neutrophils obtained from HD in presence or absence of MSCs at different time points. We demonstrated that SDS-MSCs were comparable to HD-MSCs in supporting the viability of neutrophils. More importantly, SDS-MSC were able to produce high amount of IL-6, a crucial cytokine involved in the protection of neutrophils from apoptosis. In addition, a genome wide gene expression analysis was carried out using HG-U133 Plus 2.0 Arrays. Results showed a SDS-MSCs specific profile, significantly different from HD-MSCs. All the genes, differentially expressed in mesenchymal cells obtained from Shwachman patients, are involved in the embryogenesis and in the development of different organs. In conclusion, we successfully isolated and characterized MSCs from 27 SDS patients. Further studies are needed to better comprehend the functional and molecular features of SDS-MSCs, which are potentially involved in the hematological abnormalities typical of SDS patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Does the Inhibition of Valosin Containing Protein (VCP) Has an Effect on Apoptosis of Bone Marrow Mesenchymal Stem Cells Derived from Acute Lymphoblastic Leukemia Patients and Healthy Donors?

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1576
Author(s):  
Şeyma Kipel ◽  
Hilal Nakkaş ◽  
Sevil Çaylı ◽  
Yasin Köksal ◽  
Habibe Meltem Özgüner
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Acute Lymphoblastic Leukemia ◽  
Cultured Cells ◽  
Lymphoblastic Leukemia ◽  
Data Availability ◽  
Cancer Type ◽  
Healthy Donors ◽  
Cancer Types

Acute lymphoblastic leukemia (ALL) is the most common cancer type observed in childhood. Bone marrow (BM) microenvironment has significant role both at the beginning and the progress of leukemic period. Mesenchymal stem cells (MSCs) that make up microenvironment, regulate growth factors, cytokines and induction of survival of ALL cells by generating intracellular signals and establishing drug resistance. p97/VCP is a type of protein and it is responsible for also intracellular ubiquitin proteasome pathway, endoplasmic-reticulum-associated protein degradation, cell cycle, apoptosis and autophagy. It is shown that p97/VCP is overexpressed in the most of the cancer types including the ALL. p97/VCP inhibitors serve as therapeutic agents. Amongst p97/VCP inhibitors, DBeQ (dibenzylquinazoline-2,4-diamine) provide to undergo apoptosis and prevents cell proliferation. In this study, MSCs obtained from ALL patients and healthy donors were isolated by density-gradient method and then these cells were cultured. Cells were incubated with DBeQ. Cell apoptosis was determined by Annexin V/PI method (in flow cytometry). According to obtained data, availability of p97/VCP inhibitor which was recommended to be used as therapeutic agent in the treatment of other cancer types, in ALL treatment will be evaluated and this study will provide a basis for future studies.

scholarly journals PKNOX2 expression and regulation in the bone marrow mesenchymal stem cells of Fanconi anemia patients and healthy donors

2018 ◽  
Vol 46 (1) ◽  
pp. 669-678 ◽  
Author(s):  
Ilgin Cagnan ◽  
Erdal Cosgun ◽  
Ozlen Konu ◽  
Duygu Uckan ◽  
Aysen Gunel-Ozcan
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Fanconi Anemia ◽  
Healthy Donors ◽  
Marrow Mesenchymal Stem Cells
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