Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa

被引：55

作者：

Rashidghamat, Ellie ^{[1
]}

Kadiyirire, Tendai ^{[1
]}

Ayis, Salma ^{[2
]}

Petrof, Gabriela ^{[5
]}

Liu, Lu ^{[6
]}

Pullabhatla, Venu ^{[7
]}

Ainali, Chrysanthi ^{[1
,9
]}

Guy, Alyson ^{[6
]}

Aristodemou, Sophia ^{[6
]}

McMillan, James R. ^{[6
]}

Ozoemena, Linda ^{[6
]}

Mee, John ^{[10
]}

Pramanik, Rashida ^{[1
]}

Saxena, Alka ^{[7
]}

Nuamah, Rosamund ^{[7
]}

de Rinaldis, Emanuele ^{[11
]}

Serrano, Sonia ^{[8
]}

Maurin, Clarisse ^{[8
]}

Martinez-Queipo, Magdalena ^{[1
]}

Lwin, Su M. ^{[1
]}

Ilic, Dusko ^{[3
]}

Martinez, Anna ^{[5
]}

Dazzi, Francesco ^{[4
]}

Slaper-Cortenbach, Ineke ^{[12
]}

Westinga, Kasper ^{[12
]}

Zeddies, Sabrina ^{[12
]}

van den Broek, Marcel ^{[12
]}

Onoufriadis, Alexandros ^{[1
]}

Mellerio, Jemima E. ^{[1
]}

McGrath, John A. ^{[1
]}

机构：

[1] Kings Coll London, St Johns Inst Dermatol, Sch Basic & Med Biosci, London, England

[2] Kings Coll London, Sch Populat Hlth & Environm Sci, London, England

[3] Kings Coll London, Fac Life Sci & Med, Dept Women & Childrens Hlth, Guys Assisted Concept Unit,Stem Cell Labs, London, England

[4] Kings Coll London, Rayne Inst, Dept Haematol Med, London, England

[5] Great Ormond St Hosp Children NHS Fdn Trust, Dept Dermatol, London, England

[6] Guys Hosp, Robin Eady Natl Diagnost Epidermolysis Bullosa La, Viapath, London, England

[7] Guys & St Thomas NHS Fdn Trust, UK NIHR GSTFT KCL Comprehens Biomed Res Ctr, London, England

[8] Guys & St Thomas NHS Fdn Trust, Clin Trial Management Res Platform, NIHR Biomed Res Ctr, London, England

[9] Dignosis Ltd, London, England

[10] St Thomas Hosp, Viapath, Immunodermatol Lab, London, England

[11] Sanofi, I&I Precis Immunol, Cambridge, MA USA

[12] Univ Med Ctr Utrecht, Dept Clin Pharm, Cell Therapy Facil, Utrecht, Netherlands

来源：

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY | 2020年 / 83卷 / 02期

关键词：

BM-MSC; epidermolysis bullosa; mesenchymal stromal cells; RDEB; IIND INTERNATIONAL-SYMPOSIUM; BONE-MARROW; STEM-CELLS; MANAGEMENT; CARCINOMA; SEVERITY; SANTIAGO; CHILE; ITCH; EB;

D O I：

10.1016/j.jaad.2019.11.038

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a hereditary blistering disorder due to a lack of type VII collagen. At present, treatment is mainly supportive. Objectives: To determine whether intravenous allogeneic bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs) are safe in RDEB adults and if the cells improve wound healing and quality of life. Methods: We conducted a prospective, phase I/II, open-label study recruiting 10 RDEB adults to receive 2 intravenous infusions of BM-MSCs (on day 0 and day 14; each dose 2-4 3 106 cells/kg). Results: BM-MSCs were well tolerated with no serious adverse events to 12 months. Regarding efficacy, there was a transient reduction in disease activity scores (8/10 subjects) and a significant reduction in itch. One individual showed a transient increase in type VII collagen. Limitations: Open-label trial with no placebo. Conclusions: MSC infusion is safe in RDEB adults and can have clinical benefits for at least 2 months.

引用

页码：447 / 454

页数：8

共 50 条

[31] RESULTS FROM A PHASE I/II STUDY OF A TOPICAL GENE THERAPY (BERCOLAGENE TELSERPAVEC, B-VEC) IN PATIENTS WITH RECESSIVE DYSTROPHIC EPIDERMOLYSIS BULLOSA (RDEB)
Marinkovich, M. P.
Vinzant, Schuyler
Agarwal, Pooja
Krishna, Suma
ACTA DERMATO-VENEREOLOGICA, 2020, 100 : 48 - 48
[32] Fibroblast cell therapy enhances initial healing in recessive dystrophic epidermolysis bullosa wounds: results of a randomized, vehicle-controlled trial
Petrof, G.
Martinez-Queipo, M.
Mellerio, J. E.
Kemp, P.
McGrath, J. A.
BRITISH JOURNAL OF DERMATOLOGY, 2013, 169 (05) : 1025 - 1033
[33] Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study
Detry, Olivier
Vandermeulen, Morgan
Delbouille, Marie-Helene
Somja, Joan
Bletard, Noella
Briquet, Alexandra
Lechanteur, Chantal
Giet, Olivier
Baudoux, Etienne
Hannon, Muriel
Baron, Frederic
Beguin, Yves
JOURNAL OF HEPATOLOGY, 2017, 67 (01) : 47 - 55
[34] INVESTIGATION OF CELL THERAPY FOR RECESSIVE DYSTROPHIC EPIDERMOLYSIS BULLOSA (RDEB) THROUGH INTRADERMAL INJECTION OF ALLOGENEIC FIBROBLASTS RANDOMIZED AGAINST PLACEBO INJECTIONS OF SUSPENSION SOLUTION
Venugopal, S.
Yan, W.
Frew, J. W.
Cohn, H. I.
Tran, K.
Sturm, M.
Marinkovich, P.
Igawa, S.
Ishida-Yamamoto, A.
Murrell, D. F.
WOUND REPAIR AND REGENERATION, 2012, 20 (05) : A68 - A68
[35] Replenishment of type VII collagen and re-epithelialization of chronically ulcerated skin after intradermal administration of allogeneic mesenchymal stromal cells in two patients with recessive dystrophic epidermolysis bullosa
Conget, Paulette
Rodriguez, Fernando
Kramer, Susanne
Allers, Carolina
Simon, Valeska
Palisson, Francis
Gonzalez, Sergio
Yubero, Maria J.
CYTOTHERAPY, 2010, 12 (03) : 429 - 431
[36] Phase I / II Clinical Trial for Recessive Dystrophic Epidermolysis Bullosa Using EB-101 (COL7A1 Gene-Corrected Autologous Keratinocytes)
Tang, J. Y.
Marinkovich, M. P.
Siprashvili, Z.
Nguyen, N. T.
Gorell, E. S.
Loutit, K.
Dutt-Singkh, Y.
Barriga, M.
Solis, D.
Khuu, P.
Furukawa, L.
Lorenz, H. P.
Leung, T. H.
Keene, D. R.
Rieger, K. E.
Khavari, P. A.
Lane, A. T.
MOLECULAR THERAPY, 2018, 26 (05) : 158 - 158
[37] Reduced Intensity Conditioned Bone Marrow Transplant with Post-Transplant Cyclophosphamide and Donor-Derived Mesenchymal Stromal Cell Infusions for Recessive Dystrophic Epidermolysis Bullosa
Ebens, Christen L.
McGrath, John A.
Tamai, Katsuto
Alain, Hovnanian
Wagner, John E.
Riddle, Megan
Keene, Douglas R.
Defor, Todd E.
Tryon, Rebecca
Chen, Mei
Woodley, David T.
Hook, Kristin
Tolar, Jakub L.
BLOOD, 2018, 132
[38] INFUSION OF THIRD PARTY MESENCHYMAL STROMAL CELLS AFTER RENAL TRANSPLANTATION: A PHASE I-II OPEN-LABEL CLINICAL STUDY
Erpicum, Pauline
Weekers, Laurent
Detry, Olivier
Bonvoisin, Catherine
Delbouille, Marie-Helene
Baudoux, Etienne
Briquet, Alexandra
Gregoire, Celine
Lechanteur, Chantal
Maggipinto, Gianni
Pottel, Hans
Baron, Frederic
Jouret, Francois
Beguin, Yves
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2018, 33
[39] Safety and Feasibility of Intravenous Autologous Bone Marrow Derived Stem Cell Therapy for Patients with Acute Ischaemic Stroke: An Open-Label, Phase I Trial
Prasad, Kameshwar
Bhatia, Rohit
Mohanty, Sujata
Srivastava, M. V. Padma
Garg, Ajay
Srivastava, Achal
Goyal, Vinay
Tripathi, Manjari
Kumar, Amit
Vij, Arti
Misra, N. K.
Bal, C. S.
NEUROLOGY, 2010, 74 (09) : A509 - A510
[40] Infusion of third-party mesenchymal stromal cells after kidney transplantation: a phase I-II, open-label, clinical study
Erpicum, Pauline
Weekers, Laurent
Detry, Olivier
Bonvoisin, Catherine
Delbouille, Marie-Helene
Gregoire, Celine
Baudoux, Etienne
Briquet, Alexandra
Lechanteur, Chantal
Maggipinto, Gianni
Somja, Joan
Pottel, Hans
Baron, Frederic
Jouret, Francois
Beguin, Yves
KIDNEY INTERNATIONAL, 2019, 95 (03) : 693 - 707

← 1 2 3 4 5 →