Therapeutic angiogenesis using autologous adipose-derived regenerative cells in patients with critical limb ischaemia in Japan: a clinical pilot study

Autor: Kazumasa Unno, Yuuki Shimizu, Yuzuru Kamei, Ryo Hayashida, Ryosuke Kikuchi, Kimihiro Komori, Keisuke Takanari, Satoshi Shintani, Takeshi Katagiri, Kazuhisa Kondo, Akio Kodama, Rei Shibata, Toyoaki Murohara, Shukuro Yamaguchi
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Adult
Male
medicine.medical_specialty
Angiogenesis
Urology
Adipose tissue
Neovascularization
Physiologic
lcsh:Medicine
Pilot Projects
030204 cardiovascular system & hematology
Mesenchymal Stem Cell Transplantation
Transplantation
Autologous
Article
Neovascularization
03 medical and health sciences
Peripheral Arterial Disease
0302 clinical medicine
Japan
Ischemia
Adipocytes
Medicine
Humans
Regeneration
Therapeutic angiogenesis
Progenitor cell
lcsh:Science
Aged
Adult stem cells
Multidisciplinary
business.industry
lcsh:R
Adipose-Derived Regenerative Cells
Thromboangiitis Obliterans
Mesenchymal Stem Cells
Middle Aged
Transplantation
030104 developmental biology
Cardiovascular diseases
Adipose Tissue
Peripheral vascular disease
Angiogenesis Inducing Agents
Female
lcsh:Q
medicine.symptom
business
Adult stem cell
Stem Cell Transplantation
Zdroj: Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-020-73096-y
Popis: Adipose-derived regenerative cell (ADRC) is a promising alternative source of autologous somatic stem cells for the repair of damaged tissue. This study aimed to assess the safety and feasibility of autologous ADRC implantation for therapeutic angiogenesis in patients with critical limb ischaemia (CLI). A clinical pilot study—Therapeutic Angiogenesis by Cell Transplantation using ADRCs (TACT-ADRC) study—was initiated in Japan. Adipose tissue was obtained by ordinary liposuction method. Isolated ADRCs were injected into the ischaemic limb. We performed TACT-ADRC procedure in five patients with CLI. At 6 months, no adverse events related to the TACT-ADRC were observed. No patients required major limb amputation, and ischaemic ulcers were partly or completely healed during the 6-month follow-up. In all cases, significant clinical improvements were seen in terms of rest pain and 6-min walking distance. Numbers of circulating CD34+ and CD133+ cells markers of progenitor cell persistently increased after ADRC implantation. The ratio of VEGF-A165b (an anti-angiogenic isoform of VEGF) to total VEGF-A in plasma significantly decreased after ADRC implantation. In vitro experiments, cultured with ADRC-conditioned media (CM) resulted in increased total VEGF-A and decreased VEGF-A165b in C2C12 cells, but not in macrophages. ADRC-CM also increased CD206+ cells expression and decreased TNF-α in macrophages. Autologous ADRC implantation was safe and effective in patients with CLI and could repair damaged tissue via its ability to promote angiogenesis and suppress tissue inflammation.
Databáze: OpenAIRE
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