Bone marrow fibroblasts in patients with advanced lung cancer

Chasseing, Norma Alejandra; Hofer, Erica Leonor; Bordenave, Raúl H.; Shanley, Claudia; Rumi, L

doi:10.1590/s0100-879x2001001100014

Cited by 4 publications

(2 citation statements)

References 21 publications

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“…Other examples can be found in studies performed by Chasseing et al . (), who showed that stromal cells derived from the bone marrow of untreated lung and breast cancer patients had a deficient colony‐forming ability and were insufficient to form confluent cell layers, although the patients did not receive prior irradiation or chemotherapy (Hofer et al ., ).…”

Section: Patient‐specific Datamentioning

confidence: 99%

Qualifying stem cell sources: how to overcome potential pitfalls in regenerative medicine?

Reinke

Dienelt

Blankenstein

et al. 2014

J Tissue Eng Regen Med

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Regenerative medicine aims to replace lost cells and to restore damaged tissues and organs by either tissue-engineering approaches or stimulation of endogenous processes. Due to their biological properties, stem cells promise to be an effective source for such strategies. Especially adult multipotent stem cells (ASCs) are believed to be applicable in a broad range of therapies for the treatment of multifactorial diseases or age-related degeneration, although the molecular and cellular mechanisms underlying their regenerative function are often hardly described. Moreover, in some demanding clinical situations their efficiency remains limited. Thus, a basic understanding of ASCs regenerative function, their complex interplay with their microenvironment and how compromising conditions interfere with their efficiency is mandatory for any regenerative strategy. Concerning this matter, the impact of patient-specific constraints are often underestimated in research projects and their influence on the study results disregarded. Thus, researchers are urgently depending on well-characterized tissue samples or cells that are connected with corresponding donor information, such as secondary diseases, medication. Here, we outline principle pitfalls during experimental studies using human samples, and describe a potential strategy to overcome these challenges by establishing a core unit for cell and tissue harvesting. This facility aims to bridge the gap between clinic and research laboratories by the provision of a direct link to the clinical operating theatres. Such a strategy clearly supports basic and clinical research in the conduct of their studies and supplies highly characterized human samples together with the corresponding donor information.

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Section: Patient‐specific Datamentioning

confidence: 99%

Qualifying stem cell sources: how to overcome potential pitfalls in regenerative medicine?

Reinke

Dienelt

Blankenstein

et al. 2014

J Tissue Eng Regen Med

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“…Abnormalities in the function of CFU-F may be one of the possible mechanisms underlying metastatic processes [16][17][18][19]. In previous studies, we have found that BM from untreated advanced lung cancer patients (LCP) and breast cancer patients (BCP), without prior irradiation and chemotherapy treatments and without bone and BM metastases, had defective CFU-F as refl ected by their colony-forming effi ciency (CFE) reduction and their defi cient capacity to form confl uent layers of stromal cells [20][21][22][23]. We now hypothesize that CFU-F in LCP and BCP are under the regulation of a defective microenvironment.…”

Section: Fibroblast Colony-forming Units (Cfu-f) Assaymentioning

confidence: 99%

Mesenchymal Stromal Cells, Colony-Forming Unit Fibroblasts, From Bone Marrow of Untreated Advanced Breast and Lung Cancer Patients Suppress Fibroblast Colony Formation From Healthy Marrow

Hofer

Labovsky

Russa³

et al. 2010

Stem Cells and Development

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We have shown that bone marrow (BM) from untreated advanced lung and breast cancer patients (LCP and BCP) have a reduced number of colony-forming unit fibroblasts (CFU-Fs) or mesenchymal stem cells (MSCs). Factors that regulate the proliferation and differentiation of CFU-F are produced by the patients' BM microenvironment. We have now examined whether conditioned media (CM) from patients' CFU-F-derived stromal cells also inhibits the colony-forming efficiency (CFE) of CFU-F in primary cultures from healthy volunteers (HV)-BM. Thus the number and proliferation potential of HV-CFU-F were also found to be decreased and similar to colony numbers and colony size of patients' CFU-F. Stromal cells from both of these types of colonies appeared relatively larger and lacked the characteristic spindle morphology typically seen in healthy stromal cells. We developed an arbitrary mesenchymal stromal cell maturational index by taking three measures consisting of stromal cell surface area, longitudinal and horizontal axis. All stromal indices derived from HV-CFU-F grown in patients' CM were similar to those from stromal elements derived from patients' CFU-F. These indices were markedly higher than stromal indices typical of HV-CFU-F cultured in healthy CM or standard medium [alpha-medium plus 20% heat-inactivated fetal bovine serum (FBS)]. Patients' CM had increased concentrations of the CFU-F inhibitor, GM-CSF, and low levels of bFGF and Dkk-1, strong promoters of self-renewal of MSCs, compared to the levels quantified in CM from HV-CFU-F. Moreover, the majority of patients' MSCs were unresponsive in standard medium and healthy CM to give CFU-F, indicating that the majority of mesenchymal stromal cells from patients' CFU-F are locked in maturational arrest. These results show that alterations of GM-CSF, bFGF, and Dkk-1 are associated with deficient cloning and maturation arrest of CFU-F. Defective autocrine and paracrine mechanisms may be involved in the BM microenvironments of LCP and BCP.

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Morphological Analysis and Lentiviral Transduction of Fetal Monkey Bone Marrow-Derived Mesenchymal Stem Cells

et al. 2004

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We explored the transduction kinetics of HIV-1-derived lentiviral vectors containing the CMV, EF1alpha, or PGK promoter expressing EGFP in fetal rhesus monkey bone marrow-derived mesenchymal stem cells (rhMSC). Studies included the effects of transduction (MOI 0-100) on growth, cell cycle, and differentiation toward an osteogenic lineage. Flow cytometric analysis indicated an approximate 8- to 10-fold greater quantity of EGFP-expressing rhMSC when cells were transduced with the CMV or EF1alpha promoter compared to PGK, although quantitative PCR revealed no differences at the DNA level. The CMV promoter initially expressed 10- to 100-fold higher levels of EGFP compared to EF1alpha or PGK, respectively, at increasing MOI, although a significant decline in transgene expression was observed posttransduction and with advancing passage (P < 0.01), whereas a significant increase in the level of expression was observed over time with the EF1alpha promoter. At an MOI of 100, a transient arrest at the S phase of the cell cycle was observed for both vector constructs. Transduced rhMSC differentiated toward an osteogenic lineage comparable to untransduced rhMSC and showed equivalent levels of alkaline phosphatase activity. These findings suggest that the SIN HIV-1-derived lentiviral vectors used in these studies can efficiently transduce rhMSC in vitro (CMV > EF1alpha > PGK) without inhibiting differentiation potential, although the cell cycle was transiently altered at high MOI

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Bone marrow fibroblasts in patients with advanced lung cancer

Cited by 4 publications

References 21 publications

Qualifying stem cell sources: how to overcome potential pitfalls in regenerative medicine?

Qualifying stem cell sources: how to overcome potential pitfalls in regenerative medicine?

Mesenchymal Stromal Cells, Colony-Forming Unit Fibroblasts, From Bone Marrow of Untreated Advanced Breast and Lung Cancer Patients Suppress Fibroblast Colony Formation From Healthy Marrow

Morphological Analysis and Lentiviral Transduction of Fetal Monkey Bone Marrow-Derived Mesenchymal Stem Cells

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