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Phase I/IIa Feasibility Trial of Autologous Quality- and Quantity-Cultured Peripheral Blood Mononuclear Cell Therapy for Non-Healing Extremity Ulcers

Non-healing wounds are among the main causes of morbidity and mortality. We recently described a novel, serum-free ex vivo expansion system, the quantity and quality culture system (QQc), which uses peripheral blood mononuclear cells (PBMNCs) for effective and noninvasive regeneration of tissue and...

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Autores principales: Tanaka, Rica, Fujimura, Satoshi, Kado, Makiko, Fukuta, Taro, Arita, Kayo, Hirano-Ito, Rie, Mita, Tomoya, Watada, Hirotaka, Kato, Yoshiteru, Miyauchi, Katsumi, Mizuno, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929435/
https://www.ncbi.nlm.nih.gov/pubmed/35298656
http://dx.doi.org/10.1093/stcltm/szab018
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author Tanaka, Rica
Fujimura, Satoshi
Kado, Makiko
Fukuta, Taro
Arita, Kayo
Hirano-Ito, Rie
Mita, Tomoya
Watada, Hirotaka
Kato, Yoshiteru
Miyauchi, Katsumi
Mizuno, Hiroshi
author_facet Tanaka, Rica
Fujimura, Satoshi
Kado, Makiko
Fukuta, Taro
Arita, Kayo
Hirano-Ito, Rie
Mita, Tomoya
Watada, Hirotaka
Kato, Yoshiteru
Miyauchi, Katsumi
Mizuno, Hiroshi
author_sort Tanaka, Rica
collection PubMed
description Non-healing wounds are among the main causes of morbidity and mortality. We recently described a novel, serum-free ex vivo expansion system, the quantity and quality culture system (QQc), which uses peripheral blood mononuclear cells (PBMNCs) for effective and noninvasive regeneration of tissue and vasculature in murine and porcine models. In this prospective clinical study, we investigated the safety and efficacy of QQ-cultured peripheral blood mononuclear cell (MNC-QQ) therapy for chronic non-healing ischemic extremity wounds. Peripheral blood was collected from 9 patients with 10 chronic (>1 month) non-healing wounds (8 males, 1 female; 64-74 years) corresponding to ischemic extremity ulcers. PBMNCs were isolated and cultured using QQc. Within a 20-cm area surrounding the ulcer, 2 × 10(7) cells were injected under local anesthesia. Wound healing was monitored photometrically every 2 weeks. The primary endpoint was safety, whereas the secondary endpoint was efficacy at 12-week post-injection. All patients remained ambulant, and no deaths, other serious adverse events, or major amputations were observed for 12 weeks after cell transplantation. Six of the 10 cases showed complete wound closure with an average wound closure rate of 73.2% ± 40.1% at 12 weeks. MNC-QQ therapy increased vascular perfusion, skin perfusion pressure, and decreased pain intensity in all patients. These results indicate the feasibility and safety of MNC-QQ therapy in patients with chronic non-healing ischemic extremity wounds. As the therapy involves transplanting highly vasculogenic cells obtained from a small blood sample, it may be an effective and highly vasculogenic strategy for limb salvage.
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spelling pubmed-89294352022-03-18 Phase I/IIa Feasibility Trial of Autologous Quality- and Quantity-Cultured Peripheral Blood Mononuclear Cell Therapy for Non-Healing Extremity Ulcers Tanaka, Rica Fujimura, Satoshi Kado, Makiko Fukuta, Taro Arita, Kayo Hirano-Ito, Rie Mita, Tomoya Watada, Hirotaka Kato, Yoshiteru Miyauchi, Katsumi Mizuno, Hiroshi Stem Cells Transl Med Human Clinical Article Non-healing wounds are among the main causes of morbidity and mortality. We recently described a novel, serum-free ex vivo expansion system, the quantity and quality culture system (QQc), which uses peripheral blood mononuclear cells (PBMNCs) for effective and noninvasive regeneration of tissue and vasculature in murine and porcine models. In this prospective clinical study, we investigated the safety and efficacy of QQ-cultured peripheral blood mononuclear cell (MNC-QQ) therapy for chronic non-healing ischemic extremity wounds. Peripheral blood was collected from 9 patients with 10 chronic (>1 month) non-healing wounds (8 males, 1 female; 64-74 years) corresponding to ischemic extremity ulcers. PBMNCs were isolated and cultured using QQc. Within a 20-cm area surrounding the ulcer, 2 × 10(7) cells were injected under local anesthesia. Wound healing was monitored photometrically every 2 weeks. The primary endpoint was safety, whereas the secondary endpoint was efficacy at 12-week post-injection. All patients remained ambulant, and no deaths, other serious adverse events, or major amputations were observed for 12 weeks after cell transplantation. Six of the 10 cases showed complete wound closure with an average wound closure rate of 73.2% ± 40.1% at 12 weeks. MNC-QQ therapy increased vascular perfusion, skin perfusion pressure, and decreased pain intensity in all patients. These results indicate the feasibility and safety of MNC-QQ therapy in patients with chronic non-healing ischemic extremity wounds. As the therapy involves transplanting highly vasculogenic cells obtained from a small blood sample, it may be an effective and highly vasculogenic strategy for limb salvage. Oxford University Press 2022-02-26 /pmc/articles/PMC8929435/ /pubmed/35298656 http://dx.doi.org/10.1093/stcltm/szab018 Text en © The Author(s) 2022. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Human Clinical Article
Tanaka, Rica
Fujimura, Satoshi
Kado, Makiko
Fukuta, Taro
Arita, Kayo
Hirano-Ito, Rie
Mita, Tomoya
Watada, Hirotaka
Kato, Yoshiteru
Miyauchi, Katsumi
Mizuno, Hiroshi
Phase I/IIa Feasibility Trial of Autologous Quality- and Quantity-Cultured Peripheral Blood Mononuclear Cell Therapy for Non-Healing Extremity Ulcers
title Phase I/IIa Feasibility Trial of Autologous Quality- and Quantity-Cultured Peripheral Blood Mononuclear Cell Therapy for Non-Healing Extremity Ulcers
title_full Phase I/IIa Feasibility Trial of Autologous Quality- and Quantity-Cultured Peripheral Blood Mononuclear Cell Therapy for Non-Healing Extremity Ulcers
title_fullStr Phase I/IIa Feasibility Trial of Autologous Quality- and Quantity-Cultured Peripheral Blood Mononuclear Cell Therapy for Non-Healing Extremity Ulcers
title_full_unstemmed Phase I/IIa Feasibility Trial of Autologous Quality- and Quantity-Cultured Peripheral Blood Mononuclear Cell Therapy for Non-Healing Extremity Ulcers
title_short Phase I/IIa Feasibility Trial of Autologous Quality- and Quantity-Cultured Peripheral Blood Mononuclear Cell Therapy for Non-Healing Extremity Ulcers
title_sort phase i/iia feasibility trial of autologous quality- and quantity-cultured peripheral blood mononuclear cell therapy for non-healing extremity ulcers
topic Human Clinical Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929435/
https://www.ncbi.nlm.nih.gov/pubmed/35298656
http://dx.doi.org/10.1093/stcltm/szab018
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