Therapeutic Angiogenesis with Adipose Tissue-Derived Regenerative Cells

2017 ◽  
pp. 67-79
Author(s):  
Toyoaki Murohara ◽  
Kazuhisa Kondo
Keyword(s):  
Adipose Tissue ◽  
Therapeutic Angiogenesis ◽  
Regenerative Cells

Abstract 13143: Safety Evaluation of Therapeutic Angiogenesis With Adipose-derived Regenerative Cells for Ischemic Limb in a Tumor Bearing Model

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Junya Suzuki ◽  
Yuuki Shimizu ◽  
Kazuhito Tsuzuki ◽  
Zhongyue Pu ◽  
Shukuro Yamaguchi ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Imaging System ◽  
Lymphatic Vessels ◽  
Blood Perfusion ◽  
Capillary Density ◽  
Therapeutic Angiogenesis ◽  
Control Group ◽  
In Vivo Bioluminescence Imaging ◽  
Regenerative Cells

Introduction: Implantation of adipose-derived regenerative cells (ADRC) is a promising novel strategy to augment angiogenesis and blood perfusion recovery in ischemic diseases with no other therapeutic option. However, there is a clinical concern underlying therapeutic angiogenesis that implantation of ADRC may promote tumor growth and metastasis via remote angiogenesis. Accordingly, we tested whether therapeutic angiogenesis with ADRC against hindlimb ischemia (HLI) would affect remote tumor growth and angiogenesis in a tumor-bearing mouse ischemic hindlimb model. Methods and results: B16F10-Luc (murine melanoma cells expressing luciferase, 1x106 cells/animal) were implanted to C57BL/6J mice’s (male, 8-10 weeks old, n=10) back. Mice were subjected to unilateral HLI surgery one day after tumor implantation. Then, mice were randomly assigned to the control group or the ADRC group (n=5 for each). ADRC (1x106 cells/animal) or PBS were implanted/injected into ischemic hindlimb muscles one day after the surgery. Blood perfusion recovery in HLI by laser Doppler perfusion imaging system and tumor size by a caliper were measured every week up to 21 days after surgery. At POD 21, tumor weight and luciferase activity in primary tumors obtained by in vivo bioluminescence imaging system were also evaluated. Immunohistochemistry by CD31 or LYVE1 staining was performed to detect feeder arteries or outflow lymphatic vessels in tumors. The results demonstrated that better blood perfusion recovery and more capillary density in HLI was observed in the ADRC group than in the control group (p<0.05, respectively). However, there were no significant differences in terms of tumor volume (p=0.95), tumor weight (p=0.88) and luciferase activity of primary tumor (p=0.92) between those two groups. No sign of distant metastasis was detected by macroscopic and pathological examination, and by in vivo bioluminescence imaging system in both groups. Further study also revealed that capillary density of peritumoral blood vessels or lymphatic vessels was not augmented by ADRC implantation into remote HLI. Conclusions: Our data indicated that therapeutic angiogenesis with ADRC implantation against HLI did not promote remote tumor growth, angiogenesis and metastasis.

No influence on tumor growth by intramuscular injection of adipose-derived regenerative cells: safety evaluation of therapeutic angiogenesis with cell therapy

2020 ◽  
Author(s):  
Junya Suzuki ◽  
Yuuki Shimizu ◽  
Kazuhito Tsuzuki ◽  
Zhongyue Pu ◽  
Shingo Narita ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Hind Limb ◽  
Lymphatic Vessels ◽  
Blood Perfusion ◽  
Limb Ischemia ◽  
Therapeutic Angiogenesis ◽  
Tissue Ischemia ◽  
Regenerative Cells ◽  
Ischemic Diseases

Therapeutic angiogenesis with autologous stem/progenitor cells is a promising novel strategy for treatment of severe ischemic diseases. Human clinical trials utilizing autologous adipose-derived regenerative cells (ADRCs) have not reported treatment-related critical adverse effects thus far. However, there is still a large knowledge gap whether treatment of ischemic diseases with angiogenic therapy using ADRCs would promote unfavorable angiogenesis associated with tumors in vivo. Herein, we addressed this clinical question using a mouse hind limb ischemia (HLI) and simultaneous remote tumor implantation model. C57BL/6J background wild-type mice were injected with murine B16F10 melanoma cells on their back, one day before ischemic surgery. These mice were subjected to surgical unilateral hindlimb ischemia, followed by ADRCs implantation or PBS injection into the hindlimb ischemic muscles on the next day. Intramuscular implantation of ADRCs enhanced tissue capillary density and blood flow examined by a laser Doppler blood perfusion analysis in hind limb. However, this therapeutic regimen for ischemic limb using ADRCs did not affect remote melanoma growth nor the density of its feeder artery, angiogenesis and lymphatic vessels compared to the PBS group. In addition, no distant metastases were detected in any of the mice regardless the group. In conclusion, local implantation of ADRCs promotes angiogenesis in response to tissue ischemia in the hind limb without promoting remote tumor growth and related angio/lymphangiogenesis. Therapeutic angiogenesis to the ischemic hind limb using ADRCs seems to be safe regarding remote tumor growth.

scholarly journals New Mechanical Fat Separation Technique: Adjustable Regenerative Adipose-tissue Transfer (ARAT) and Mechanical Stromal Cell Transfer (MEST)

2020 ◽  
Vol 2 (4) ◽  
Author(s):  
H Eray Copcu ◽  
Sule Oztan
Keyword(s):  
Adipose Tissue ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Retention Rate ◽  
High Rate ◽  
Cell Transfer ◽  
Fat Tissue ◽  
Cell Counts ◽  
Tissue Transfer ◽  
Regenerative Cells

Abstract Background Adipose tissue is not only a very important source of filler but also the body’s greatest source of regenerative cells. Objectives In this study, adipose tissue was cut to the desired dimensions using ultra-sharp blade systems to avoid excessive blunt pressure and applied to various anatomical areas—a procedure known as adjustable regenerative adipose-tissue transfer (ARAT). Mechanical stromal cell transfer (MEST) of regenerative cells from fat tissue was also examined. Methods ARAT, MEST, or a combination of these was applied in the facial area of a total of 24 patients who were followed for at least 24 months. The integrity of the fat tissue cut with different diameter blades is shown histopathologically. The number and viability of the stromal cells obtained were evaluated and secretome analyses were performed. Patient and surgeon satisfaction were assessed with a visual analog scale. Results With the ARAT technique, the desired size fat grafts were obtained between 4000- and 200-micron diameters and applied at varying depths to different aesthetic units of the face, and a guide was developed. In MEST, stromal cells were obtained from 100 mL of condensed fat using different indication-based protocols with 93% mean viability and cell counts of 28.66 to 88.88 × 106. Conclusions There are 2 main complications in fat grafting: visibility in thin skin and a low retention rate. The ARAT technique can be used to prevent these 2 complications. MEST, on the other hand, obtains a high rate of fat and viable stromal cells without applying excessive blunt pressure. Level of Evidence: 4

Autologous Adipose-Derived Regenerative Cells for Therapeutic Angiogenesis

2009 ◽  
Vol 15 (24) ◽  
pp. 2784-2790 ◽  
Author(s):  
Toyoaki Murohara ◽  
Satoshi Shintani ◽  
Kazuhisa Kondo
Keyword(s):  
Therapeutic Angiogenesis ◽  
Regenerative Cells

scholarly journals Isolation of adipose tissue derived regenerative cells from human subcutaneous tissue with or without the use of an enzymatic reagent

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0221457 ◽  
Author(s):  
Glenn E. Winnier ◽  
Nick Valenzuela ◽  
Jennifer Peters-Hall ◽  
Joshua Kellner ◽  
Christopher Alt ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Subcutaneous Tissue ◽  
Regenerative Cells

scholarly journals VEGF secretion by adipose tissue-derived regenerative cells is impaired under hyperglycemic conditions via glucose transporter activation and ROS increase

2014 ◽  
Vol 35 (6) ◽  
pp. 397-405
Author(s):  
Hiromi MATSUGAMI ◽  
Yusuke HARADA ◽  
Yasutaka KURATA ◽  
Yasutaka YAMAMOTO ◽  
Yuki OTSUKI ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Transporter ◽  
Regenerative Cells
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