PMID- 33636546
OWN - NLM
STAT- MEDLINE
DCOM- 20210917
LR  - 20211110
IS  - 1873-2534 (Electronic)
IS  - 0165-2427 (Linking)
VI  - 234
DP  - 2021 Apr
TI  - Effects of continuous passage on the immunomodulatory properties of equine bone 
      marrow-derived mesenchymal stem cells in vitro.
PG  - 110203
LID - S0165-2427(21)00021-0 [pii]
LID - 10.1016/j.vetimm.2021.110203 [doi]
AB  - BACKGROUND: The immunomodulatory properties of mesenchymal stem cells (MSCs) have 
      been studied extensively due to their increasing clinical application for tissue 
      regeneration and repair following culture expansion. We have studied the effect 
      of continuous passage on the immunomodulatory capacity of equine bone 
      marrow-derived MSCs (BM-MSCs). Equine BM-MSCs were isolated and culture expanded 
      to passage three, six, and nine (P3, P6, P9). Immunomodulatory properties of each 
      passage were assessed using a T cell proliferation assay and cytokine synthesis 
      following stimulation with interferon gamma (IFN-gamma). RESULTS: Equine BM-MSCs 
      maintained their primary cell morphology and immunophenotype throughout all 
      passages. T cell proliferation was suppressed by all passages of BM-MSCs, 
      compared to peripheral blood mononuclear cells (PBMCs) alone. There was no 
      significant difference in suppression of T cell proliferation between P3, P6, and 
      P9 BM-MSCs. All passages of BM-MSCs significantly increased cytokine synthesis in 
      response to stimulation with IFN-gamma. There were no significant differences in 
      production of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) or 
      regulate on activation, normal T cell expressed and secreted (RANTES) following 
      stimulation with IFN-gamma between P3, P6, and P9 BM-MSCs. P9 BM-MSCs had 
      significantly increased production of tumor necrosis factor alpha (TNF-alpha), 
      (IL-1beta), and (IL-10) compared to P3 BM-MSCs. Additionally, there was a 
      significant increase in production of (IL-8) in P6 and P9 BM-MSCs in comparison 
      to P3 BM-MSCs. CONCLUSIONS: Our findings demonstrate that culture expansion 
      affects some of the immunomodulatory properties of BM-MSCs in vitro, which may 
      suggest that MSCs isolated from a single collection of bone marrow may be culture 
      expanded, but only those from lower passage numbers would be ideal for clinical 
      application.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Connard, Shannon S
AU  - Connard SS
AD  - Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, 
      University of Pennsylvania, Philadelphia, PA, United States.
FAU - Linardi, Renata L
AU  - Linardi RL
AD  - Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, 
      University of Pennsylvania, Philadelphia, PA, United States.
FAU - Even, Kayla M
AU  - Even KM
AD  - Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, 
      University of Pennsylvania, Philadelphia, PA, United States.
FAU - Berglund, Alix K
AU  - Berglund AK
AD  - Department of Clinical Sciences, College of Veterinary Medicine and the 
      Comparative Medicine Institute, North Carolina State University, Raleigh, NC, 
      United States.
FAU - Schnabel, Lauren V
AU  - Schnabel LV
AD  - Department of Clinical Sciences, College of Veterinary Medicine and the 
      Comparative Medicine Institute, North Carolina State University, Raleigh, NC, 
      United States.
FAU - Ortved, Kyla F
AU  - Ortved KF
AD  - Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, 
      University of Pennsylvania, Philadelphia, PA, United States. Electronic address: 
      kortved@vet.upenn.edu.
LA  - eng
PT  - Journal Article
DEP - 20210212
PL  - Netherlands
TA  - Vet Immunol Immunopathol
JT  - Veterinary immunology and immunopathology
JID - 8002006
RN  - 0 (Cytokines)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
EIN - Vet Immunol Immunopathol. 2021 Dec;242:110340. PMID: 34756666
MH  - Animals
MH  - Bone Marrow Cells/drug effects/immunology/physiology
MH  - Cell Differentiation/drug effects/*immunology
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Cytokines/analysis/biosynthesis/*immunology
MH  - Female
MH  - Horses
MH  - *Immunomodulation
MH  - In Vitro Techniques
MH  - Interferon-gamma/pharmacology
MH  - Lymphocyte Activation/drug effects/immunology
MH  - Male
MH  - Mesenchymal Stem Cells/*immunology/physiology
OTO - NOTNLM
OT  - Continuous passage
OT  - Horse
OT  - Immunomodulation
OT  - Mesenchymal stem cells
EDAT- 2021/02/27 06:00
MHDA- 2021/09/18 06:00
CRDT- 2021/02/26 20:14
PHST- 2020/10/28 00:00 [received]
PHST- 2021/02/01 00:00 [revised]
PHST- 2021/02/05 00:00 [accepted]
PHST- 2021/02/27 06:00 [pubmed]
PHST- 2021/09/18 06:00 [medline]
PHST- 2021/02/26 20:14 [entrez]
AID - S0165-2427(21)00021-0 [pii]
AID - 10.1016/j.vetimm.2021.110203 [doi]
PST - ppublish
SO  - Vet Immunol Immunopathol. 2021 Apr;234:110203. doi: 10.1016/j.vetimm.2021.110203. 
      Epub 2021 Feb 12.