Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia

Junji Moriya, Tohru Minamino, Kaoru Tateno, Naomi Shimizu, Yoichi Kuwabara, Yasunori Sato, Yasushi Saito, Issei Komuro

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Background-Injection of bone marrow mononuclear cells has been reported to promote neovascularization of ischemic tissues effectively. We found that peripheral blood mononuclear cells were as efficient as bone marrow mononuclear cells for the treatment of limb ischemia in animals and showed that this treatment was feasible and safe in no-option patients with limb ischemia. However, the long-term outcome of such therapy has not been investigated. Methods and Results-We retrospectively analyzed the data for 42 patients who were treated between July 2002 and December 2005 by using the log-rank test, the Kaplan-Meier method, and the Cox proportional hazard model. Improvement of ischemic symptoms was observed in 60% to 70% of the patients. The annual rate of major amputation was decreased markedly by treatment. Improvement of ischemic symptoms was less marked in arteriosclerosis obliterans (ASO) patients on dialysis compared with nonhemodialysis ASO or thromboangiitis obliterans patients. Indeed, the survival rate of these patients was lower than that of nonhemodialysis ASO or thromboangiitis obliterans patients. Major adverse events such as death, major amputation, and cardiovascular events occurred mostly in ASO patients, and most of them were on dialysis. There was no significant difference in the cardiovascular event-free rate between responders and nonresponders. The survival rate of younger responders was better than that of nonresponders. Conclusions-Although this study was not placebo-controlled and these initial results were from a retrospective analysis, injection of peripheral blood mononuclear cells might be safe and potentially effective for the treatment of limb ischemia, but caution is needed when managing ASO patients on dialysis.

Original languageEnglish
Pages (from-to)245-254
Number of pages10
JournalCirculation: Cardiovascular Interventions
Volume2
Issue number3
DOIs
Publication statusPublished - 2009 Jun 1
Externally publishedYes

Fingerprint

Blood Cells
Arteriosclerosis Obliterans
Ischemia
Extremities
Thromboangiitis Obliterans
Dialysis
Therapeutics
Amputation
Bone Marrow Cells
Survival Rate
Injections
Kaplan-Meier Estimate
Proportional Hazards Models
Placebos

Keywords

  • Angiogenesis
  • Cell therapy
  • Hemodialysis
  • Peripheral vascular disease

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia. / Moriya, Junji; Minamino, Tohru; Tateno, Kaoru; Shimizu, Naomi; Kuwabara, Yoichi; Sato, Yasunori; Saito, Yasushi; Komuro, Issei.

In: Circulation: Cardiovascular Interventions, Vol. 2, No. 3, 01.06.2009, p. 245-254.

Research output: Contribution to journalArticle

Moriya, Junji ; Minamino, Tohru ; Tateno, Kaoru ; Shimizu, Naomi ; Kuwabara, Yoichi ; Sato, Yasunori ; Saito, Yasushi ; Komuro, Issei. / Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia. In: Circulation: Cardiovascular Interventions. 2009 ; Vol. 2, No. 3. pp. 245-254.
@article{c097cab5e073441aa98bee2265c50ef1,
title = "Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia",
abstract = "Background-Injection of bone marrow mononuclear cells has been reported to promote neovascularization of ischemic tissues effectively. We found that peripheral blood mononuclear cells were as efficient as bone marrow mononuclear cells for the treatment of limb ischemia in animals and showed that this treatment was feasible and safe in no-option patients with limb ischemia. However, the long-term outcome of such therapy has not been investigated. Methods and Results-We retrospectively analyzed the data for 42 patients who were treated between July 2002 and December 2005 by using the log-rank test, the Kaplan-Meier method, and the Cox proportional hazard model. Improvement of ischemic symptoms was observed in 60{\%} to 70{\%} of the patients. The annual rate of major amputation was decreased markedly by treatment. Improvement of ischemic symptoms was less marked in arteriosclerosis obliterans (ASO) patients on dialysis compared with nonhemodialysis ASO or thromboangiitis obliterans patients. Indeed, the survival rate of these patients was lower than that of nonhemodialysis ASO or thromboangiitis obliterans patients. Major adverse events such as death, major amputation, and cardiovascular events occurred mostly in ASO patients, and most of them were on dialysis. There was no significant difference in the cardiovascular event-free rate between responders and nonresponders. The survival rate of younger responders was better than that of nonresponders. Conclusions-Although this study was not placebo-controlled and these initial results were from a retrospective analysis, injection of peripheral blood mononuclear cells might be safe and potentially effective for the treatment of limb ischemia, but caution is needed when managing ASO patients on dialysis.",
keywords = "Angiogenesis, Cell therapy, Hemodialysis, Peripheral vascular disease",
author = "Junji Moriya and Tohru Minamino and Kaoru Tateno and Naomi Shimizu and Yoichi Kuwabara and Yasunori Sato and Yasushi Saito and Issei Komuro",
year = "2009",
month = "6",
day = "1",
doi = "10.1161/CIRCINTERVENTIONS.108.799361",
language = "English",
volume = "2",
pages = "245--254",
journal = "Circulation: Cardiovascular Interventions",
issn = "1941-7640",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia

AU - Moriya, Junji

AU - Minamino, Tohru

AU - Tateno, Kaoru

AU - Shimizu, Naomi

AU - Kuwabara, Yoichi

AU - Sato, Yasunori

AU - Saito, Yasushi

AU - Komuro, Issei

PY - 2009/6/1

Y1 - 2009/6/1

N2 - Background-Injection of bone marrow mononuclear cells has been reported to promote neovascularization of ischemic tissues effectively. We found that peripheral blood mononuclear cells were as efficient as bone marrow mononuclear cells for the treatment of limb ischemia in animals and showed that this treatment was feasible and safe in no-option patients with limb ischemia. However, the long-term outcome of such therapy has not been investigated. Methods and Results-We retrospectively analyzed the data for 42 patients who were treated between July 2002 and December 2005 by using the log-rank test, the Kaplan-Meier method, and the Cox proportional hazard model. Improvement of ischemic symptoms was observed in 60% to 70% of the patients. The annual rate of major amputation was decreased markedly by treatment. Improvement of ischemic symptoms was less marked in arteriosclerosis obliterans (ASO) patients on dialysis compared with nonhemodialysis ASO or thromboangiitis obliterans patients. Indeed, the survival rate of these patients was lower than that of nonhemodialysis ASO or thromboangiitis obliterans patients. Major adverse events such as death, major amputation, and cardiovascular events occurred mostly in ASO patients, and most of them were on dialysis. There was no significant difference in the cardiovascular event-free rate between responders and nonresponders. The survival rate of younger responders was better than that of nonresponders. Conclusions-Although this study was not placebo-controlled and these initial results were from a retrospective analysis, injection of peripheral blood mononuclear cells might be safe and potentially effective for the treatment of limb ischemia, but caution is needed when managing ASO patients on dialysis.

AB - Background-Injection of bone marrow mononuclear cells has been reported to promote neovascularization of ischemic tissues effectively. We found that peripheral blood mononuclear cells were as efficient as bone marrow mononuclear cells for the treatment of limb ischemia in animals and showed that this treatment was feasible and safe in no-option patients with limb ischemia. However, the long-term outcome of such therapy has not been investigated. Methods and Results-We retrospectively analyzed the data for 42 patients who were treated between July 2002 and December 2005 by using the log-rank test, the Kaplan-Meier method, and the Cox proportional hazard model. Improvement of ischemic symptoms was observed in 60% to 70% of the patients. The annual rate of major amputation was decreased markedly by treatment. Improvement of ischemic symptoms was less marked in arteriosclerosis obliterans (ASO) patients on dialysis compared with nonhemodialysis ASO or thromboangiitis obliterans patients. Indeed, the survival rate of these patients was lower than that of nonhemodialysis ASO or thromboangiitis obliterans patients. Major adverse events such as death, major amputation, and cardiovascular events occurred mostly in ASO patients, and most of them were on dialysis. There was no significant difference in the cardiovascular event-free rate between responders and nonresponders. The survival rate of younger responders was better than that of nonresponders. Conclusions-Although this study was not placebo-controlled and these initial results were from a retrospective analysis, injection of peripheral blood mononuclear cells might be safe and potentially effective for the treatment of limb ischemia, but caution is needed when managing ASO patients on dialysis.

KW - Angiogenesis

KW - Cell therapy

KW - Hemodialysis

KW - Peripheral vascular disease

UR - http://www.scopus.com/inward/record.url?scp=77953677951&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953677951&partnerID=8YFLogxK

U2 - 10.1161/CIRCINTERVENTIONS.108.799361

DO - 10.1161/CIRCINTERVENTIONS.108.799361

M3 - Article

C2 - 20031722

AN - SCOPUS:77953677951

VL - 2

SP - 245

EP - 254

JO - Circulation: Cardiovascular Interventions

JF - Circulation: Cardiovascular Interventions

SN - 1941-7640

IS - 3

ER -