Placenta-derived multipotent mesenchymal stromal cells: a promising potential cell-based therapy for canine inflammatory brain disease
Rogério Martins Amorim,Rogério Martins Amorim,Kaitlin C. Clark,Naomi J. Walker,Priyadarsini Kumar,Kyle Herout,Dori L. Borjesson,Aijun Wang +7 more
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TLDR
It is demonstrated that ASCs and PMSCs have substantial in vitro potential as a cell-based therapy for IBD; however, PM SCs more potently inhibited lymphocyte proliferation by inducing apoptosis of activated lymphocytes.Abstract:
Canine inflammatory brain disease (IBD) is a severe inflammatory disorder characterized by infiltration of activated immune cell subsets into the brain and spinal cord. Multipotent mesenchymal stromal cells (MSCs) are a promising therapy for IBD, based on their potent pro-angiogenic, neuroprotective, and immunomodulatory properties. The aims of this study were to compare the immunomodulatory attributes of canine adipose-derived MSCs (ASCs) and placenta-derived MSCs (PMSCs) in vitro. These data will serve as potency information to help inform the optimal MSC cell source to treat naturally occurring canine IBD. Indoleamine 2,3 dioxygenase (IDO) activity and prostaglandin E2 (PGE2) concentration at baseline and after stimulation with interferon gamma (IFNγ) and/or tumor necrosis factor alpha (TNFα) were measured from canine ASC and PMSC cultures. Leukocyte suppression assays (LSAs) were performed to compare the ability of ASCs and PMSCs to inhibit activated peripheral blood mononuclear cell (PBMC) proliferation. IDO activity and PGE2; interleukin (IL)-2, IL-6, and IL-8; TNFα; and vascular endothelial growth factor (VEGF) concentrations were also measured from co-culture supernatants. Cell cycle analysis was performed to determine how ASCs and PMSCs altered lymphocyte proliferation. Activated canine MSCs from both tissue sources secreted high concentrations of IDO and PGE2, after direct stimulation with IFNγ and TNFα, or indirect stimulation by activated PBMCs. Both ASCs and PMSCs inhibited activated PBMC proliferation in LSA assays; however, PMSCs inhibited PBMC proliferation significantly more than ASCs. Blocking PGE2 and IDO in LSA assays determined that PGE2 is important only for ASC inhibition of PBMC proliferation. Activated ASCs increased IL-6 and VEGF secretion and decreased TNFα secretion, while activated PMSCs increased IL-6, IL-8, and VEGF secretion. ASCs inhibited lymphocyte proliferation via cell cycle arrest in the G0/G1 and PMSCs inhibited lymphocyte proliferation via induction of lymphocyte apoptosis. Our results demonstrate that ASCs and PMSCs have substantial in vitro potential as a cell-based therapy for IBD; however, PMSCs more potently inhibited lymphocyte proliferation by inducing apoptosis of activated lymphocytes. These data suggest that the mechanism by which ASCs and PMSCs downregulate PBMC proliferation differs. Additional studies may elucidate additional mechanisms by which canine MSCs modulate neuroinflammatory responses.read more
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3D-printed nerve guidance conduits multi-functionalized with canine multipotent mesenchymal stromal cells promote neuroregeneration after sciatic nerve injury in rats.
Diego Noé Rodríguez-Sánchez,Giovana Boff Araujo Pinto,Luciana Politti Cartarozzi,Alexandre Leite Rodrigues de Oliveira,Ana Lívia de Carvalho Bovolato,Márcio de Carvalho,Jorge Vicente Lopes da Silva,Janaina Dernowsek,Marjorie de Assis Golim,Benedito Barraviera,Rui Seabra Ferreira,Elenice Deffune,Mathues Bertanha,Rogério Martins Amorim +13 more
TL;DR: The authors' multimodal approach, support the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats, and is associated with a shift in the regeneration process towards the formation of myelinated fibers.
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3D spheroids of human placenta-derived mesenchymal stem cells attenuate spinal cord injury in mice.
Junhao Deng,Li Miao,Li Miao,Fanqi Meng,Liu Zhongyang,Song Wang,Song Wang,Yuan Zhang,Li Ming,Zhirui Li,Licheng Zhang,Peifu Tang +11 more
TL;DR: Wang et al. as discussed by the authors found that 3D human placenta-derived mesenchymal stem cells (3D-HPMSCs) exhibited a significant increase in secretion of anti-inflammatory factors and trophic factors like VEGF, PDGF, FGF, and showed great potentials on angiogenesis and neurite morphogenesis.
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The Multi-Therapeutic Role of MSCs in Diabetic Nephropathy.
Yi Wang,Su-Kang Shan,Bei Guo,Fuxingzi Li,Ming-Hui Zheng,Li-Min Lei,Qiu-Shuang Xu,Muhammad Hasnain Ehsan Ullah,Feng Xu,Xiao Lin,Ling-Qing Yuan +10 more
TL;DR: In this article, a review summarizes several mechanisms of mesenchymal stem cells, especially MSCs derived exosomes in diabetic nephropathy therapy, including hyperglycemia regulation, antiinflammatory, anti-fibrosis, pro-angiogenesis, and renal function protection.
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The Unique Properties of Placental Mesenchymal Stromal Cells: A Novel Source of Therapy for Congenital and Acquired Spinal Cord Injury.
Edwin Kulubya,Kaitlin C. Clark,Kaitlin C. Clark,Dake Hao,Dake Hao,Sabrina Lazar,Sabrina Lazar,Arash Ghaffari-Rafi,Tejas Karnati,Julius O. Ebinu,Marike Zwienenberg,Diana L. Farmer,Diana L. Farmer,Aijun Wang,Aijun Wang +14 more
TL;DR: In this paper, the mesenchymal stem/stromal cells (PMSCs) have been shown to exhibit unique neuroprotective, angiogenic, and antioxidant properties, all which are promising applications for SCI.
Journal ArticleDOI
Therapeutic efficacy of human adipose mesenchymal stem cells in Crohn’s colon fibrosis is improved by IFN-γ and kynurenic acid priming through indoleamine 2,3-dioxygenase-1 signaling
Yixin Ye,Xiaomei Zhang,Dongsheng Su,Yushuang Ren,Fuyi Cheng,Yunqi Yao,Gang Shi,Ya-ru Ji,Shuang Chen,Pengyi Shi,Lei Dai,Xiaolan Su,Hongxin Deng +12 more
TL;DR: In this article , human adipose-derived MSCs (hADSCs) were pretreated in vitro with IFN-γ and kynurenic acid (KYNA) to promote indoleamine 2,3dioxygenase-1 (IDO-1) signaling, providing a potential protocol to treat IBD and fibrosis disease.
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