PMID- 36951952
OWN - NLM
STAT- MEDLINE
DCOM- 20230509
LR  - 20230608
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 8
IP  - 9
DP  - 2023 May 8
TI  - Local administration of mesenchymal stromal cells is safe and modulates the 
      immune compartment in ulcerative proctitis.
LID - 10.1172/jci.insight.167402 [doi]
LID - e167402
AB  - BACKGROUNDDue to their immunoregulatory and tissue regenerative features, 
      mesenchymal stromal cells (MSCs) are a promising novel tool for the management of 
      ulcerative proctitis (UP). Here we report on a phase IIa clinical study that 
      evaluated the impact of local MSC therapy on UP.METHODSThirteen refractory UP 
      patients, with an endoscopic Mayo score (EMS) of 2 or 3, were included. Seven 
      patients received 20-40 million allogeneic MSCs (cohort 1), while 6 patients 
      received 40-80 million MSCs (cohort 2). Adverse events (AEs) were assessed at 
      baseline and on weeks 2, 6, 12, and 24. Clinical, endoscopic, and biochemical 
      parameters were assessed at baseline and on weeks 2 and 6. Furthermore, we 
      evaluated the engraftment of MSCs, the presence of donor-specific human leukocyte 
      antigen (HLA) antibodies (DSAs), and we determined the impact of MSC therapy on 
      the local immune compartment.RESULTSNo serious AEs were observed. The clinical 
      Mayo score was significantly improved on weeks 2 and 6, and the EMS was 
      significantly improved on week 6, compared with baseline. On week 6, donor MSCs 
      were still detectable in rectal biopsies from 4 of 9 patients and DSAs against 
      both HLA class I and class II were found. Mass cytometry showed a reduction in 
      activated CD8+ T cells and CD16+ monocytes and an enrichment in mononuclear 
      phagocytes and natural killer cells in biopsies after local MSC 
      therapy.CONCLUSIONLocal administration of allogeneic MSCs is safe, tolerable, and 
      feasible for treatment of refractory UP and shows encouraging signs of clinical 
      efficacy and modulation of local immune responses. This sets the stage for larger 
      clinical trials.TRIAL REGISTRATIONEU Clinical Trials Register (EudraCT, 
      2017-003524-75) and the Dutch Trial Register (NTR7205).FUNDINGECCO grant 2020.
FAU - Ouboter, Laura F
AU  - Ouboter LF
AD  - Department of Gastroenterology and Hepatology.
AD  - Department of Immunology.
FAU - Barnhoorn, Marieke C
AU  - Barnhoorn MC
AD  - Department of Gastroenterology and Hepatology.
FAU - Verspaget, Hein W
AU  - Verspaget HW
AD  - Department of Gastroenterology and Hepatology.
FAU - Plug, Leonie
AU  - Plug L
AD  - Department of Gastroenterology and Hepatology.
FAU - Pool, Emma S
AU  - Pool ES
AD  - Department of Hematology, and.
FAU - Szuhai, Karoly
AU  - Szuhai K
AD  - Department of Cell and Chemical Biology, Leiden University Medical Center, 
      Leiden, Netherlands.
FAU - Hawinkels, Lukas Jac
AU  - Hawinkels LJ
AD  - Department of Gastroenterology and Hepatology.
FAU - van Pel, Melissa
AU  - van Pel M
AD  - Department of Immunology.
AD  - Netherlands Center for the Clinical Advancement of Stem Cell & Gene Therapies 
      (NECSTGEN), Leiden, Netherlands.
AD  - Department of Internal Medicine, Leiden University Medical Center, Leiden, 
      Netherlands.
FAU - Zwaginga, Jaap Jan
AU  - Zwaginga JJ
AD  - Department of Internal Medicine, Leiden University Medical Center, Leiden, 
      Netherlands.
FAU - Roelen, Dave
AU  - Roelen D
AD  - Department of Immunology.
FAU - Koning, Frits
AU  - Koning F
AD  - Department of Immunology.
FAU - Pascutti, M Fernanda
AU  - Pascutti MF
AD  - Department of Immunology.
FAU - van der Meulen-de Jong, Andrea E
AU  - van der Meulen-de Jong AE
AD  - Department of Gastroenterology and Hepatology.
LA  - eng
SI  - EudraCT/2017-003524-75
SI  - NTR/NTR7205
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230508
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Humans
MH  - *Mesenchymal Stem Cell Transplantation/adverse effects
MH  - *Mesenchymal Stem Cells
MH  - *Colitis, Ulcerative/therapy
MH  - Histocompatibility Antigens Class I
MH  - *Proctitis/therapy
PMC - PMC10243829
OTO - NOTNLM
OT  - Clinical Trials
OT  - Inflammation
OT  - Inflammatory bowel disease
EDAT- 2023/03/24 06:00
MHDA- 2023/05/09 06:42
PMCR- 2023/05/08
CRDT- 2023/03/23 12:03
PHST- 2022/11/22 00:00 [received]
PHST- 2023/03/17 00:00 [accepted]
PHST- 2023/05/09 06:42 [medline]
PHST- 2023/03/24 06:00 [pubmed]
PHST- 2023/03/23 12:03 [entrez]
PHST- 2023/05/08 00:00 [pmc-release]
AID - 167402 [pii]
AID - 10.1172/jci.insight.167402 [doi]
PST - epublish
SO  - JCI Insight. 2023 May 8;8(9):e167402. doi: 10.1172/jci.insight.167402.