Allogeneic ABCB5+ Mesenchymal Stem Cells for Treatment-Refractory Chronic Venous Ulcers: A Phase I/IIa Clinical Trial
A significant number of chronic venous ulcers (CVUs) fail to heal despite guideline-conform standards of care. Skin-derived ABCB5+ mesenchymal stem cells can dampen the sustained IL-1β‒driven inflammation present in chronic wounds. On the basis of their wound healing‒facilitating effects in a mouse...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Elsevier
2022
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/30269062a0c04e579251c083a6768869 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:30269062a0c04e579251c083a6768869 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:30269062a0c04e579251c083a67688692021-11-20T05:15:52ZAllogeneic ABCB5+ Mesenchymal Stem Cells for Treatment-Refractory Chronic Venous Ulcers: A Phase I/IIa Clinical Trial2667-026710.1016/j.xjidi.2021.100067https://doaj.org/article/30269062a0c04e579251c083a67688692022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2667026721000680https://doaj.org/toc/2667-0267A significant number of chronic venous ulcers (CVUs) fail to heal despite guideline-conform standards of care. Skin-derived ABCB5+ mesenchymal stem cells can dampen the sustained IL-1β‒driven inflammation present in chronic wounds. On the basis of their wound healing‒facilitating effects in a mouse CVU model and an autologous first-in-human study, ABCB5+ mesenchymal stem cells have emerged as a potential candidate for cell-based advanced therapy of nonhealing CVUs. In this interventional, multicenter, single-arm, phase I/IIa clinical trial, subjects whose CVUs had emerged as standard therapy resistant received one or two topical applications of 1 × 106 allogeneic ABCB5+ mesenchymal stem cells per cm2 wound area, in addition to standard treatment. Of 83 treatment-emergent adverse events, only three were judged related to the cell product; they were mild or moderate and recovered without sequelae. Wound size markedly decreased from baseline to week 12, resulting in a median wound size reduction of 76% (full analysis set, n = 31), 78% (per-protocol set, n = 27), and 87% (subset of responders, n = 21). In conclusion, the study treatment was well-tolerated and safe. The treatment elicited a profound wound size reduction within 12 weeks, identifying ABCB5+ mesenchymal stem cells as a potential candidate for adjunctive therapy of otherwise incurable CVUs. These results justify the conduct of a larger, randomized, controlled trial to confirm clinical efficacy.Andreas KerstanKathrin DieterElke Niebergall-RothAnn-Kathrin DachtlerKorinna KraftMarkus StückerGeorg DaeschleinMichael JüngerTobias GörgeUlrich Meyer-PannwittCornelia Erfurt-BergeCharlotte von EngelhardtAndreas KlareChristiane PfeifferJasmina EsterlechnerHannes M. SchröderMartin GasserAna M. Waaga-GasserMatthias GoebelerSeda BallikayaSamar SadeghiGeorge F. MurphyDennis P. OrgillNatasha Y. FrankChristoph GanssKarin Scharffetter-KochanekMarkus H. FrankMark A. KluthElsevierarticleDermatologyRL1-803ENJID Innovations, Vol 2, Iss 1, Pp 100067- (2022) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Dermatology RL1-803 |
| spellingShingle |
Dermatology RL1-803 Andreas Kerstan Kathrin Dieter Elke Niebergall-Roth Ann-Kathrin Dachtler Korinna Kraft Markus Stücker Georg Daeschlein Michael Jünger Tobias Görge Ulrich Meyer-Pannwitt Cornelia Erfurt-Berge Charlotte von Engelhardt Andreas Klare Christiane Pfeiffer Jasmina Esterlechner Hannes M. Schröder Martin Gasser Ana M. Waaga-Gasser Matthias Goebeler Seda Ballikaya Samar Sadeghi George F. Murphy Dennis P. Orgill Natasha Y. Frank Christoph Ganss Karin Scharffetter-Kochanek Markus H. Frank Mark A. Kluth Allogeneic ABCB5+ Mesenchymal Stem Cells for Treatment-Refractory Chronic Venous Ulcers: A Phase I/IIa Clinical Trial |
| description |
A significant number of chronic venous ulcers (CVUs) fail to heal despite guideline-conform standards of care. Skin-derived ABCB5+ mesenchymal stem cells can dampen the sustained IL-1β‒driven inflammation present in chronic wounds. On the basis of their wound healing‒facilitating effects in a mouse CVU model and an autologous first-in-human study, ABCB5+ mesenchymal stem cells have emerged as a potential candidate for cell-based advanced therapy of nonhealing CVUs. In this interventional, multicenter, single-arm, phase I/IIa clinical trial, subjects whose CVUs had emerged as standard therapy resistant received one or two topical applications of 1 × 106 allogeneic ABCB5+ mesenchymal stem cells per cm2 wound area, in addition to standard treatment. Of 83 treatment-emergent adverse events, only three were judged related to the cell product; they were mild or moderate and recovered without sequelae. Wound size markedly decreased from baseline to week 12, resulting in a median wound size reduction of 76% (full analysis set, n = 31), 78% (per-protocol set, n = 27), and 87% (subset of responders, n = 21). In conclusion, the study treatment was well-tolerated and safe. The treatment elicited a profound wound size reduction within 12 weeks, identifying ABCB5+ mesenchymal stem cells as a potential candidate for adjunctive therapy of otherwise incurable CVUs. These results justify the conduct of a larger, randomized, controlled trial to confirm clinical efficacy. |
| format |
article |
| author |
Andreas Kerstan Kathrin Dieter Elke Niebergall-Roth Ann-Kathrin Dachtler Korinna Kraft Markus Stücker Georg Daeschlein Michael Jünger Tobias Görge Ulrich Meyer-Pannwitt Cornelia Erfurt-Berge Charlotte von Engelhardt Andreas Klare Christiane Pfeiffer Jasmina Esterlechner Hannes M. Schröder Martin Gasser Ana M. Waaga-Gasser Matthias Goebeler Seda Ballikaya Samar Sadeghi George F. Murphy Dennis P. Orgill Natasha Y. Frank Christoph Ganss Karin Scharffetter-Kochanek Markus H. Frank Mark A. Kluth |
| author_facet |
Andreas Kerstan Kathrin Dieter Elke Niebergall-Roth Ann-Kathrin Dachtler Korinna Kraft Markus Stücker Georg Daeschlein Michael Jünger Tobias Görge Ulrich Meyer-Pannwitt Cornelia Erfurt-Berge Charlotte von Engelhardt Andreas Klare Christiane Pfeiffer Jasmina Esterlechner Hannes M. Schröder Martin Gasser Ana M. Waaga-Gasser Matthias Goebeler Seda Ballikaya Samar Sadeghi George F. Murphy Dennis P. Orgill Natasha Y. Frank Christoph Ganss Karin Scharffetter-Kochanek Markus H. Frank Mark A. Kluth |
| author_sort |
Andreas Kerstan |
| title |
Allogeneic ABCB5+ Mesenchymal Stem Cells for Treatment-Refractory Chronic Venous Ulcers: A Phase I/IIa Clinical Trial |
| title_short |
Allogeneic ABCB5+ Mesenchymal Stem Cells for Treatment-Refractory Chronic Venous Ulcers: A Phase I/IIa Clinical Trial |
| title_full |
Allogeneic ABCB5+ Mesenchymal Stem Cells for Treatment-Refractory Chronic Venous Ulcers: A Phase I/IIa Clinical Trial |
| title_fullStr |
Allogeneic ABCB5+ Mesenchymal Stem Cells for Treatment-Refractory Chronic Venous Ulcers: A Phase I/IIa Clinical Trial |
| title_full_unstemmed |
Allogeneic ABCB5+ Mesenchymal Stem Cells for Treatment-Refractory Chronic Venous Ulcers: A Phase I/IIa Clinical Trial |
| title_sort |
allogeneic abcb5+ mesenchymal stem cells for treatment-refractory chronic venous ulcers: a phase i/iia clinical trial |
| publisher |
Elsevier |
| publishDate |
2022 |
| url |
https://doaj.org/article/30269062a0c04e579251c083a6768869 |
| work_keys_str_mv |
AT andreaskerstan allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT kathrindieter allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT elkeniebergallroth allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT annkathrindachtler allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT korinnakraft allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT markusstucker allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT georgdaeschlein allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT michaeljunger allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT tobiasgorge allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT ulrichmeyerpannwitt allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT corneliaerfurtberge allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT charlottevonengelhardt allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT andreasklare allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT christianepfeiffer allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT jasminaesterlechner allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT hannesmschroder allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT martingasser allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT anamwaagagasser allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT matthiasgoebeler allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT sedaballikaya allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT samarsadeghi allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT georgefmurphy allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT dennisporgill allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT natashayfrank allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT christophganss allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT karinscharffetterkochanek allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT markushfrank allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial AT markakluth allogeneicabcb5mesenchymalstemcellsfortreatmentrefractorychronicvenousulcersaphaseiiiaclinicaltrial |
| _version_ |
1718419473915969536 |