Lung tissue engineering technique with adipose stromal cells improves surgical outcome for pulmonary emphysema

Norihisa Shigemura, Meinoshin Okumura, Shinya Mizuno, Yukiko Imanishi, Akifumi Matsuyama, Hiroyuki Shiono, Toshikazu Nakamura, Yoshiki Sawa

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Rationale and Objectives: Hepatocyte growth factor (HGF) is a potent regenerative factor generated after a lung injury, and HGF supplementation after surgical reduction has been shown to enhance compensatory growth in remnant lungs and improve pathophysiologic conditions in a rat model of emphysema. Adipose tissue-derived stromal cells (ASCs) produce a large amount of angiogenic factors, including HGF. After lung volume reduction surgery (LVRS), we treated rats by implanting HGF-secreting ASCs with a scaffold onto the remnant lung tissue to determine the usefulness of this technique for treating respiratory dysfunction. Methods and Main Results: Cells were isolated from rat inguinal adipose tissue and characterized by flow cytometry. ASCs were cultured on a polyglycolic acid felt sheet as a sealant material, and were shown to secrete significantly greater amounts of HGF than other angiogenic factors. Next, ASCs on polyglycolic acid felt sheets were used to cover the cut edge of the remaining lungs after LVRS for emphysema in rats. One week after implantation of the ASCs, both alveolar and vascular regeneration were significantly accelerated as compared with the rats that underwent LVRS alone. Consequently, gas exchange and exercise tolerance were also significantly restored, with these good results persisting for more than 1 mo. Conclusions: The present findings demonstrate the therapeutic potential of cell therapy using ASCs with a scaffold for selective delivery of HGF to remnant lungs, which resulted in enhancement of compensatory growth, after surgical resection. This approach may provide a new strategy for lung tissue engineering to improve LVRS outcome.

Original languageEnglish
Pages (from-to)1199-1205
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume174
Issue number11
DOIs
Publication statusPublished - 01-12-2006

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Pulmonary Emphysema
Tissue Engineering
Stromal Cells
Hepatocyte Growth Factor
Adipose Tissue
Pneumonectomy
Lung
Polyglycolic Acid
Angiogenesis Inducing Agents
Emphysema
Exercise Tolerance
Groin
Lung Injury
Growth
Cell- and Tissue-Based Therapy
Blood Vessels
Regeneration
Flow Cytometry
Gases

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Shigemura, Norihisa ; Okumura, Meinoshin ; Mizuno, Shinya ; Imanishi, Yukiko ; Matsuyama, Akifumi ; Shiono, Hiroyuki ; Nakamura, Toshikazu ; Sawa, Yoshiki. / Lung tissue engineering technique with adipose stromal cells improves surgical outcome for pulmonary emphysema. In: American Journal of Respiratory and Critical Care Medicine. 2006 ; Vol. 174, No. 11. pp. 1199-1205.
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abstract = "Rationale and Objectives: Hepatocyte growth factor (HGF) is a potent regenerative factor generated after a lung injury, and HGF supplementation after surgical reduction has been shown to enhance compensatory growth in remnant lungs and improve pathophysiologic conditions in a rat model of emphysema. Adipose tissue-derived stromal cells (ASCs) produce a large amount of angiogenic factors, including HGF. After lung volume reduction surgery (LVRS), we treated rats by implanting HGF-secreting ASCs with a scaffold onto the remnant lung tissue to determine the usefulness of this technique for treating respiratory dysfunction. Methods and Main Results: Cells were isolated from rat inguinal adipose tissue and characterized by flow cytometry. ASCs were cultured on a polyglycolic acid felt sheet as a sealant material, and were shown to secrete significantly greater amounts of HGF than other angiogenic factors. Next, ASCs on polyglycolic acid felt sheets were used to cover the cut edge of the remaining lungs after LVRS for emphysema in rats. One week after implantation of the ASCs, both alveolar and vascular regeneration were significantly accelerated as compared with the rats that underwent LVRS alone. Consequently, gas exchange and exercise tolerance were also significantly restored, with these good results persisting for more than 1 mo. Conclusions: The present findings demonstrate the therapeutic potential of cell therapy using ASCs with a scaffold for selective delivery of HGF to remnant lungs, which resulted in enhancement of compensatory growth, after surgical resection. This approach may provide a new strategy for lung tissue engineering to improve LVRS outcome.",
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Lung tissue engineering technique with adipose stromal cells improves surgical outcome for pulmonary emphysema. / Shigemura, Norihisa; Okumura, Meinoshin; Mizuno, Shinya; Imanishi, Yukiko; Matsuyama, Akifumi; Shiono, Hiroyuki; Nakamura, Toshikazu; Sawa, Yoshiki.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 174, No. 11, 01.12.2006, p. 1199-1205.

Research output: Contribution to journalArticle

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T1 - Lung tissue engineering technique with adipose stromal cells improves surgical outcome for pulmonary emphysema

AU - Shigemura, Norihisa

AU - Okumura, Meinoshin

AU - Mizuno, Shinya

AU - Imanishi, Yukiko

AU - Matsuyama, Akifumi

AU - Shiono, Hiroyuki

AU - Nakamura, Toshikazu

AU - Sawa, Yoshiki

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N2 - Rationale and Objectives: Hepatocyte growth factor (HGF) is a potent regenerative factor generated after a lung injury, and HGF supplementation after surgical reduction has been shown to enhance compensatory growth in remnant lungs and improve pathophysiologic conditions in a rat model of emphysema. Adipose tissue-derived stromal cells (ASCs) produce a large amount of angiogenic factors, including HGF. After lung volume reduction surgery (LVRS), we treated rats by implanting HGF-secreting ASCs with a scaffold onto the remnant lung tissue to determine the usefulness of this technique for treating respiratory dysfunction. Methods and Main Results: Cells were isolated from rat inguinal adipose tissue and characterized by flow cytometry. ASCs were cultured on a polyglycolic acid felt sheet as a sealant material, and were shown to secrete significantly greater amounts of HGF than other angiogenic factors. Next, ASCs on polyglycolic acid felt sheets were used to cover the cut edge of the remaining lungs after LVRS for emphysema in rats. One week after implantation of the ASCs, both alveolar and vascular regeneration were significantly accelerated as compared with the rats that underwent LVRS alone. Consequently, gas exchange and exercise tolerance were also significantly restored, with these good results persisting for more than 1 mo. Conclusions: The present findings demonstrate the therapeutic potential of cell therapy using ASCs with a scaffold for selective delivery of HGF to remnant lungs, which resulted in enhancement of compensatory growth, after surgical resection. This approach may provide a new strategy for lung tissue engineering to improve LVRS outcome.

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