Treatment of Cutaneous Ulcers with Multilayered Mixed Sheets of Autologous Fibroblasts and Peripheral Blood Mononuclear Cells

Background/Aims: We have developed a mixed-cell sheet consisting of autologous fibroblasts and peripheral blood mononuclear cells with a high potency for angiogenesis and wound healing against refractory cutaneous ulcers in mouse and rabbit models. To increase the effectiveness of the mixed sheet, we developed a multilayered mixed sheet. Methods: We assessed the therapeutic effects of multilayered sheets on cutaneous ulcers in mice. Growth factors and chemokines were assessed by enzyme-linked immunosorbent assay. Angiogenesis and fibroblast migration were measured by using tube formation and migration assays. Wound healing rate of cutaneous ulcers was evaluated in mice with diabetes mellitus. Results: The concentration of secreted vascular endothelial growth factor, hepatocyte growth factor, transforming growth factor, C-X-C motif chemokine ligand (CXCL)-1, and CXCL-2 in multilayered sheets was much higher than that in single-layered mixed-cell sheets (single-layered sheets) and multilayered sheets of fibroblasts alone (fibroblast sheets). The supernatant in multilayered sheets enhanced angiogenic potency and fibroblast migration compared with single-layered and fibroblast sheets in an in vitro experiment. The wound healing rate in the multilayered sheet-treated group was higher compared with the no-treatment group (control) at the early stage of healing. Moreover, both vessel lumen area and microvessel density in tissues treated with multilayered sheets were significantly increased compared with tissues in the control group. Conclusion: Multilayered sheets promoted wound healing and microvascular angiogenesis in the skin by supplying growth factors and cytokines. Accordingly, our data suggest that multilayered sheets may be a promising therapeutic material for refractory cutaneous ulcers.

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Altered expression of vascular endothelial growth factor, vascular endothelial growth factor receptor-1, vascular endothelial growth factor receptor-2, and Soluble Fms-like Tyrosine Kinase-1 in peripheral blood mononuclear cells from normal and preeclamptic pregnancies

The Chinese Journal of Physiology ◽

10.4103/cjp.cjp_15_19 ◽

2019 ◽

Vol 62 (3) ◽

pp. 117 ◽

Cited By ~ 2

Author(s):

Zaima Ali ◽

Saba Khaliq ◽

Saima Zaki ◽

HafizUsman Ahmad ◽

KhalidPervaiz Lone

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Peripheral Blood Mononuclear Cells ◽

Mononuclear Cells ◽

Growth Factor Receptor ◽

Vascular Endothelial ◽

Peripheral Blood Mononuclear ◽

Altered Expression ◽

Blood Mononuclear Cells ◽

Endothelial Growth Factor

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A Growth Factor-Free Co-Culture System of Osteoblasts and Peripheral Blood Mononuclear Cells for the Evaluation of the Osteogenesis Potential of Melt-Electrowritten Polycaprolactone Scaffolds

International Journal of Molecular Sciences ◽

10.3390/ijms20051068 ◽

2019 ◽

Vol 20 (5) ◽

pp. 1068 ◽

Cited By ~ 8

Author(s):

Andreas Hammerl ◽

Carlos Diaz Cano ◽

Elena De-Juan-Pardo ◽

Martijn van Griensven ◽

Patrina Poh

Keyword(s):

Growth Factor ◽

Bone Regeneration ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Culture System ◽

Mononuclear Cells ◽

Regeneration Potential ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

Scaffolds made of biodegradable biomaterials are widely used to guide bone regeneration. Commonly, in vitro assessment of scaffolds’ osteogenesis potential has been performed predominantly in monoculture settings. Hence, this study evaluated the potential of an unstimulated, growth factor-free co-culture system comprised of osteoblasts (OB) and peripheral blood mononuclear cells (PBMC) over monoculture of OB as an in vitro platform for screening of bone regeneration potential of scaffolds. Particularly, this study focuses on the osteogenic differentiation and mineralized matrix formation aspects of cells. The study was performed using scaffolds fabricated by means of a melt electrowriting (MEW) technique made of medical-grade polycaprolactone (PCL), with or without a surface coating of calcium phosphate (CaP). Qualitative results, i.e., cell morphology by fluorescence imaging and matrix mineralization by von Kossa staining, indicated the differences in cell behaviours in response to scaffolds’ biomaterial. However, no obvious differences were noted between OB and OB+PBMC groups. Hence, quantitative investigation, i.e., alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) activities, and gene expression were quantitatively evaluated by reverse transcription-polymerase chain reaction (RT-qPCR), were evaluated only of PCL/CaP scaffolds cultured with OB+PBMC, while PCL/CaP scaffolds cultured with OB or PBMC acted as a control. Although this study showed no differences in terms of osteogenic differentiation and ECM mineralization, preliminary qualitative results indicate an obvious difference in the cell/non-mineralized ECM density between scaffolds cultured with OB or OB+PBMC that could be worth further investigation. Collectively, the unstimulated, growth factor-free co-culture (OB+PBMC) system presented in this study could be beneficial for the pre-screening of scaffolds’ in vitro bone regeneration potential prior to validation in vivo.

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Abnormal Regulation of Insulin-Like Growth Factor Gene Expression in Peripheral Blood Mononuclear Cells from Patients with IgA Nephropathy

American Journal of Nephrology ◽

10.1159/000168463 ◽

1992 ◽

Vol 12 (5) ◽

pp. 292-302 ◽

Cited By ~ 5

Author(s):

Tsukasa Nakamura ◽

Isao Ehihara ◽

Isao Nagaoka ◽

Toshimasa Takahashi ◽

Yasuhiko Tomino ◽

...

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Iga Nephropathy ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Factor Gene ◽

Growth Factor Gene ◽

Blood Mononuclear Cells

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MicroRNA-93 may control vascular endothelial growth factor A in circulating peripheral blood mononuclear cells in acute Kawasaki disease

Pediatric Research ◽

10.1038/pr.2016.93 ◽

2016 ◽

Vol 80 (3) ◽

pp. 425-432 ◽

Cited By ~ 13

Author(s):

Kazuyoshi Saito ◽

Hideyuki Nakaoka ◽

Ichiro Takasaki ◽

Keiichi Hirono ◽

Seiji Yamamoto ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Kawasaki Disease ◽

Peripheral Blood Mononuclear Cells ◽

Mononuclear Cells ◽

Vascular Endothelial ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Acute Kawasaki Disease ◽

Endothelial Growth Factor

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Transforming Growth Factor-Beta Differentially Regulates the Adhesiveness of Normal and Psoriatic Dermal Microvascular Endothelial Cells for Peripheral Blood Mononuclear Cells

Journal of Investigative Dermatology ◽

10.1111/1523-1747.ep12499836 ◽

1992 ◽

Vol 98 (4) ◽

pp. 405-409 ◽

Cited By ~ 12

Author(s):

Jian-Ping Cai ◽

Vincent Falanga ◽

J Richard Taylor ◽

Yee-Hon Chin

Keyword(s):

Endothelial Cells ◽

Growth Factor ◽

Peripheral Blood Mononuclear Cells ◽

Transforming Growth Factor Beta ◽

Mononuclear Cells ◽

Transforming Growth Factor ◽

Microvascular Endothelial Cells ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Growth Factor Beta

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Peripheral blood mononuclear cells from patients with systemic sclerosis spontaneously secrete increased amounts of vascular endothelial growth factor (VEGF) already in the early stage of the disease

Advances in Medical Sciences ◽

10.2478/v10039-011-0025-z ◽

2011 ◽

Vol 56 (2) ◽

pp. 255-263 ◽

Cited By ~ 15

Author(s):

M Bielecki ◽

K Kowal ◽

A Lapinska ◽

S Chwiesko-Minarowska ◽

L Chyczewski ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Systemic Sclerosis ◽

Growth Factor ◽

Peripheral Blood Mononuclear Cells ◽

Mononuclear Cells ◽

Early Stage ◽

Vascular Endothelial ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Endothelial Growth Factor

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Transforming Growth Factor β1 Production by CD4+ CD25+ Regulatory T Cells in Peripheral Blood Mononuclear Cells from Healthy Subjects Stimulated with Leishmania guyanensis

Infection and Immunity ◽

10.1128/iai.73.9.5908-5914.2005 ◽

2005 ◽

Vol 73 (9) ◽

pp. 5908-5914 ◽

Cited By ~ 15

Author(s):

A. Kariminia ◽

E. Bourreau ◽

H. Pascalis ◽

P. Couppié ◽

D. Sainte-Marie ◽

...

Keyword(s):

T Cells ◽

Growth Factor ◽

Healthy Subjects ◽

Mononuclear Cells ◽

Transforming Growth Factor ◽

Suppressive Activity ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Leishmania Guyanensis ◽

Tgf Β1

ABSTRACT Transforming growth factor β (TGF-β) has been shown to be a central immunomodulator used by leishmaniae to escape effective mechanisms of protection in human and murine infections with these parasites. However, all the information is derived from studies of established infection, while little is known about TGF-β production in response to Leishmania stimulation in healthy subjects. In this study, TGF-β1 production was demonstrated in peripheral blood mononuclear cells from healthy subjects never exposed to leishmaniae in response to live Leishmania guyanensis, and the TGF-β1-producing cells were described as a distinct subpopulation of CD4+ CD25+ regulatory T cells. The suppressive properties of CD4+ CD25+ T cells were demonstrated in vitro by their inhibition of production of interleukin 2 (IL-2) and IL-10 by CD4+ CD25− T cells in the presence of either anti-CD3 or L. guyanensis. Although neutralization of TGF-β1 did not reverse the suppressive activity of CD4+ CD25+ T cells activated by anti-CD3, it reversed the suppressive activity of CD4+ CD25+ T cells activated by L. guyanensis. Altogether our data demonstrated that TGF-β1 is involved in the suppressive activity of L. guyanensis-stimulated CD4+ CD25+ T cells from healthy controls.

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