scholarly journals Inability of Low Oxygen Tension to Induce Chondrogenesis in Human Infrapatellar Fat Pad Mesenchymal Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Samia Rahman ◽  
Alexander R. A. Szojka ◽  
Yan Liang ◽  
Melanie Kunze ◽  
Victoria Goncalves ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Oxygen Tension ◽  
Endochondral Ossification ◽  
Infrapatellar Fat Pad ◽  
Low Oxygen ◽  
Fat Pad ◽  
Chondrogenic Medium ◽  
Low Oxygen Tension

ObjectiveArticular cartilage of the knee joint is avascular, exists under a low oxygen tension microenvironment, and does not self-heal when injured. Human infrapatellar fat pad-sourced mesenchymal stem cells (IFP-MSC) are an arthroscopically accessible source of mesenchymal stem cells (MSC) for the repair of articular cartilage defects. Human IFP-MSC exists physiologically under a low oxygen tension (i.e., 1–5%) microenvironment. Human bone marrow mesenchymal stem cells (BM-MSC) exist physiologically within a similar range of oxygen tension. A low oxygen tension of 2% spontaneously induced chondrogenesis in micromass pellets of human BM-MSC. However, this is yet to be demonstrated in human IFP-MSC or other adipose tissue-sourced MSC. In this study, we explored the potential of low oxygen tension at 2% to drive the in vitro chondrogenesis of IFP-MSC. We hypothesized that 2% O2 will induce stable chondrogenesis in human IFP-MSC without the risk of undergoing endochondral ossification at ectopic sites of implantation.MethodsMicromass pellets of human IFP-MSC were cultured under 2% O2 or 21% O2 (normal atmosphere O2) in the presence or absence of chondrogenic medium with transforming growth factor-β3 (TGFβ3) for 3 weeks. Following in vitro chondrogenesis, the resulting pellets were implanted in immunodeficient athymic nude mice for 3 weeks.ResultsA low oxygen tension of 2% was unable to induce chondrogenesis in human IFP-MSC. In contrast, chondrogenic medium with TGFβ3 induced in vitro chondrogenesis. All pellets were devoid of any evidence of undergoing endochondral ossification after subcutaneous implantation in athymic mice.

scholarly journals Effect of low oxygen tension on transcriptional factor OCT4 and SOX2 expression in New Zealand rabbit bone marrow-derived mesenchymal stem cells

2020 ◽  
Vol 13 (11) ◽  
pp. 2469-2476
Author(s):  
Erma Safitri
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
New Zealand ◽  
Oxygen Tension ◽  
Culture Conditions ◽  
Low Oxygen ◽  
Sox2 Expression ◽  
Low Oxygen Tension

Background and Aim: Octamer-binding transcription factor 4 (OCT4) and sex-determining region Y-box 2 (SOX2) are transcription factors whose functions are essential to maintain the pluripotency of embryonic stem cells. The purpose of this study was to derive stem cells for in vitro culture and to maintain their viability and pluripotency, with the goal to obtain a cell line for transplantation in patients with degenerative diseases or injuries. This research focused on examining the effect of low oxygen tension on the ability of bone marrow-derived mesenchymal stem cells (BM-MSCs) to express OCT4 and SOX2 in vitro. Materials and Methods: BM-MSCs were obtained from femurs of 2000 to 3000 g New Zealand male rabbits. BM-MSCs were divided into three groups to test different culture conditions: A control group under hyperoxia condition (21% O2) and two treatment groups with low oxygen tension (1% and 3% O2). We characterized the BM-MSCs using flow cytometric measurement of cluster differentiation 44 (CD44) and cluster differentiation 90 (CD90) expression. The expression of OCT4 and SOX2 was measured by immunofluorescence staining after 48 h of incubation in chambers with normal or low oxygen tension with controlled internal atmosphere consisting of 95% N2, 5% CO2, and 1% O2 (T1) and 3% O2 (T2). We considered OCT4 and SOX2 as two markers of pluripotency induction. All immunofluorescence data were subjected to a post hoc normality Tukey's honestly significant difference test; all differences with p<5% were considered significant. Results: BM-MSCs were positive for CD44 and CD90 expression after isolation. Oxygen tension culture conditions of 1% and 3% O2 led to OCT4 and SOX2 expression on culture days 2 and 4 (p<0.05), respectively, as compared to the hyperoxia condition (21% O2). Conclusion: Based on the OCT4 and SOX2 immunofluorescence data, we conclude that the stem cells were pluripotent at low O2 tension (at 1% O2 on day 2 and at 3% O2 on day 4), whereas under 21% O2 the OCT4 and SOX2 were not expressed.

Effects of in vitro low oxygen tension preconditioning of buccal fat pad stem cells on in Vivo articular cartilage tissue repair

Life Sciences ◽  
2021 ◽  
pp. 119728
Author(s):  
Fatemeh Dehghani Nazhvani ◽  
Leila Mohammadi Amirabad ◽  
Arezo Azari ◽  
Hamid Namazi ◽  
Simzar Hosseinzadeh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Cartilage ◽  
Tissue Repair ◽  
Cartilage Tissue ◽  
Low Oxygen ◽  
Fat Pad ◽  
Buccal Fat Pad ◽  
Low Oxygen Tension

A brief very-low oxygen tension regimen is sufficient for the early chondrogenic commitment of human adipose-derived mesenchymal stem cells

2021 ◽  
Vol 66 (1) ◽  
pp. 98-104 ◽  
Author(s):  
Marco Govoni ◽  
Claudio Muscari ◽  
Francesca Bonafè ◽  
Paolo Giovanni Morselli ◽  
Marilisa Cortesi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Oxygen Tension ◽  
Low Oxygen ◽  
Low Oxygen Tension

scholarly journals Low-Oxygen Tension and IGF-I Promote Proliferation and Multipotency of Placental Mesenchymal Stem Cells (PMSCs) from Different Gestations via Distinct Signaling Pathways

Endocrinology ◽  
2014 ◽  
Vol 155 (4) ◽  
pp. 1386-1397 ◽  
Author(s):  
Amer Youssef ◽  
Cristiana Iosef ◽  
Victor K.M. Han
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Insulin Receptor ◽  
Oxygen Tension ◽  
Insulin Receptor Substrate ◽  
Low Oxygen ◽  
Insulin Receptor Substrate 1 ◽  
Placental Mesenchymal Stem Cells ◽  
Low Oxygen Tension ◽  
Igf I

The microenvironment of placental mesenchymal stem cells (PMSCs) is dynamic throughout gestation and determines changes in cell fate. In vivo, PMSCs initially develop in low-oxygen tension and low IGF-I concentrations, and both increase gradually with gestation. The impact of varying concentrations of IGF-I and changing oxygen tension on PMSC signaling and multipotency was investigated in PMSCs from early (preterm) and late (term) gestation human placentae. Preterm PMSCs had greater proliferative response to IGF-I, which was further enhanced by low-oxygen tension. Low-oxygen tension alone was sufficient to induce ERK1/2 phosphorylation, whereas IGF-I was required for AKT (protein kinase B) phosphorylation. Low-oxygen tension prolonged ERK1/2 and AKT phosphorylation with a slowed phosphorylation decay even in presence of IGF-I. Low-oxygen tension maintained higher levels of IGF-I receptor and insulin receptor substrate 1 that were otherwise decreased by exposure to IGF-I and induced a differential phosphorylation pattern on IGF-I receptorβ and insulin receptor substrate 1. Phosphorylation of ERK1/2 and AKT was different between the preterm and term PMSCs, and phospho-AKT, and not phospho-ERK1/2, was the major determinant of PMSC proliferation and octamer-4 levels. These studies demonstrate that low-oxygen tension regulates the fate of PMSCs from early and late gestations in response to IGF-I, both independently and dependently, via specific signal transduction mechanisms.

scholarly journals Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetic stability by activating glycolysis

2011 ◽  
Vol 19 (5) ◽  
pp. 743-755 ◽  
Author(s):  
J C Estrada ◽  
C Albo ◽  
A Benguría ◽  
A Dopazo ◽  
P López-Romero ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Oxygen Tension ◽  
Genetic Stability ◽  
Human Mesenchymal Stem Cells ◽  
Low Oxygen ◽  
Low Oxygen Tension

CD10/Neprilysin Enrichment in Infrapatellar Fat Pad–Derived Mesenchymal Stem Cells Under Regulatory-Compliant Conditions: Implications for Efficient Synovitis and Fat Pad Fibrosis Reversal

2020 ◽  
Vol 48 (8) ◽  
pp. 2013-2027 ◽  
Author(s):  
Dimitrios Kouroupis ◽  
Annie C. Bowles ◽  
Thomas M. Best ◽  
Lee D. Kaplan ◽  
Diego Correa
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ex Vivo ◽  
Infrapatellar Fat Pad ◽  
Therapeutic Effects ◽  
Fat Pad ◽  
In Vitro Proliferation ◽  
Differentiation Potential

Background: Synovitis and infrapatellar fat pad (IFP) fibrosis participate in various conditions of the knee. Substance P (SP), a neurotransmitter secreted within those structures and historically associated with nociception, also modulates local neurogenic inflammatory and fibrotic responses. Exposure of IFP mesenchymal stem cells (IFP-MSCs) to a proinflammatory/profibrotic environment (ex vivo priming with TNFα, IFNγ, and CTGF) induces their expression of CD10/neprilysin, effectively degrading SP in vitro and in vivo. Purpose/Hypothesis: The purpose was to test the therapeutic effects of IFP-MSCs processed under regulatory-compliant protocols, comparing them side-by-side with standard fetal bovine serum (FBS)–grown cells. The hypothesis was that when processed under such protocols, IFP-MSCs do not require ex vivo priming to acquire a CD10-rich phenotype efficiently degrading SP and reversing synovitis and IFP fibrosis. Study Design: Controlled laboratory study. Methods: Human IFP-MSCs were processed in FBS or either of 2 alternative conditions—regulatory-compliant pooled human platelet lysate (hPL) and chemically reinforced medium (Ch-R)—and then subjected to proinflammatory/profibrotic priming with TNFα, IFNγ, and CTGF. Cells were assessed for in vitro proliferation, stemness, immunophenotype, differentiation potential, transcriptional and secretory profiles, and SP degradation. Based on a rat model of acute synovitis and IFP fibrosis, the in vivo efficacy of cells degrading SP plus reversing structural signs of inflammation and fibrosis was assessed. Results: When compared with FBS, IFP-MSCs processed with either hPL or Ch-R exhibited a CD10High phenotype and showed enhanced proliferation, differentiation, and immunomodulatory transcriptional and secretory profiles (amplified by priming). Both methods recapitulated and augmented the secretion of growth factors seen with FBS plus priming, with some differences between them. Functionally, in vitro SP degradation was more efficient in hPL and Ch-R, confirmed upon intra-articular injection in vivo where CD10-rich IFP-MSCs also dramatically reversed signs of synovitis and IFP fibrosis even without priming or at significantly lower cell doses. Conclusion: hPL and Ch-R formulations can effectively replace FBS plus priming to induce specific therapeutic attributes in IFP-MSCs. The resulting fine-tuned, regulatory-compliant, cell-based product has potential future utilization as a novel minimally invasive cell therapy for the treatment of synovitis and IFP fibrosis. Clinical Relevance: The therapeutic enhancement of IFP-MSCs manufactured under regulatory-compliant conditions suggests that such a strategy could accelerate the time from preclinical to clinical phases. The therapeutic efficacy obtained at lower MSC numbers than currently needed and the avoidance of cell priming for efficient results could have a significant effect on the design of clinical protocols to potentially treat conditions involving synovitis and IFP fibrosis.

scholarly journals Low Oxygen Tension Modulates the Insulin-Like Growth Factor-1 or -2 Signaling via Both Insulin-Like Growth Factor-1 Receptor and Insulin Receptor to Maintain Stem Cell Identity in Placental Mesenchymal Stem Cells

Endocrinology ◽  
2016 ◽  
Vol 157 (3) ◽  
pp. 1163-1174 ◽  
Author(s):  
Amer Youssef ◽  
Victor K. M. Han
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Insulin Receptor ◽  
Oxygen Tension ◽  
Insulin Like Growth Factor ◽  
Low Oxygen ◽  
Placental Mesenchymal Stem Cells ◽  
Low Oxygen Tension

Abstract Placental mesenchymal stem cells (PMSCs) are readily available multipotent stem cells for potential use in regenerative therapies. For this purpose, PMSCs must be maintained in culture conditions that mimic the in vivo microenvironment. IGFs (IGF-1 and IGF-2) and oxygen tension are low in the placenta in early gestation and increase as pregnancy progresses. IGFs bind to two receptor tyrosine kinases, the IGF-1 receptor (IGF-1R) and the insulin receptor (IR), and their hybrid receptors. We hypothesized that IGF-1 and IGF-2 signal via distinct signaling pathways under low-oxygen tension to maintain PMSC multipotency. In preterm PMSCs, low-oxygen tension increased the expression of IGF-2 and reduced IGF-1. IGF-1 stimulated higher phosphorylation of IGF-1Rβ, ERK1/2, and AKT, which was maintained at steady lower levels by low oxygen tension. PMSC proliferation was increased by IGF-1 more than IGF-2,and was potentiated by low-oxygen tension. This IGF/low oxygen tension-mediated proliferation was receptor dependent because neutralization of the IGF-1R inhibited PMSC proliferation in the presence of IGF-1 and the IR in presence of IGF-2. These findings suggest that both IGF-1R and the IR can participate in mediating IGF signaling in maintaining PMSCs multipotency. We conclude that low-oxygen tension can modify the IGF-1 or IGF-2 signaling via the IGF-1R and IR in PMSCs.

Low oxygen tension reveals distinct HOX codes in human cord blood-derived stromal cells associated with specific endochondral ossification capacities in vitro and in vivo

2016 ◽  
Vol 11 (10) ◽  
pp. 2725-2736 ◽  
Author(s):  
Stefanie Liedtke ◽  
Benedetto Sacchetti ◽  
Anita Laitinen ◽  
Samantha Donsante ◽  
Robert Klöckers ◽  
...  
Keyword(s):  
Cord Blood ◽  
Oxygen Tension ◽  
Stromal Cells ◽  
Endochondral Ossification ◽  
Low Oxygen ◽  
Human Cord Blood ◽  
Low Oxygen Tension

Low Oxygen Tension is Critical for the Culture of Human Mesenchymal Stem Cells with Strong Osteogenic Potential from Haemarthrosis Fluid

2013 ◽  
Vol 9 (5) ◽  
pp. 599-608 ◽  
Author(s):  
Callie A. Knuth ◽  
Marcia E. Clark ◽  
Annette P. Meeson ◽  
Sameer K. Khan ◽  
Daniel J. Dowen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Oxygen Tension ◽  
Human Mesenchymal Stem Cells ◽  
Osteogenic Potential ◽  
Low Oxygen ◽  
Low Oxygen Tension

scholarly journals Effect of low oxygen tension on the biological characteristics of human bone marrow mesenchymal stem cells

2016 ◽  
Vol 21 (6) ◽  
pp. 1089-1099 ◽  
Author(s):  
Dae Seong Kim ◽  
Young Jong Ko ◽  
Myoung Woo Lee ◽  
Hyun Jin Park ◽  
Yoo Jin Park ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Oxygen Tension ◽  
Biological Characteristics ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Low Oxygen ◽  
Low Oxygen Tension ◽  
Marrow Mesenchymal Stem Cells
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