Characteristics and Immunomodulating Functions of Adipose-Derived and Bone Marrow-Derived Mesenchymal Stem Cells Across Defined Human Leukocyte Antigen Barriers

Abstract

BackgroundVascularized composite allotransplantation opens new possibilities in reconstructive transplantation such as hand or face transplants. Lifelong immunosuppression and its side-effects are the main drawbacks of this procedure. Mesenchymal stem cells (MSCs) have clinically useful immunomodulatory effects and may be able to reduce the burden of chronic immunosuppression. Herein, we assess and compare characteristics and immunomodulatory capacities of bone marrow- and adipose tissue-derived MSCs isolated from the same human individual across defined human leukocyte antigen (HLA) barriers.Materials and methodsSamples of omental (o.) adipose tissue, subcutaneous (s.c.) adipose tissue, and bone marrow aspirate from 10 human organ donors were retrieved and MSCs isolated. Cells were characterized by flow cytometry and differentiated in three lineages: adipogenic, osteogenic, and chondrogenic. In mixed lymphocyte reactions, the ability of adipose-derived mesenchymal stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (BMSCs) to suppress the immune response was assessed and compared within individual donors. HLA mismatched or mitogen stimulations were analyzed in co-culture with different MSC concentrations. Supernatants were analyzed for cytokine contents.ResultsAll cell types, s.c.ASC, o.ASC, and BMSC demonstrated individual differentiation potential and cell surface markers. Immunomodulating effects were dependent on dose and cell passage. Proliferation of responder cells was most effectively suppressed by s.c.ASCs and combination with BMSC resulted in highly efficient immunomodulation. Immunomodulation was not cell contact-dependent and cells demonstrated a specific cytokine secretion.ConclusionWhen human ASCs and BMSCs are isolated from the same individual, both show effective immunomodulation across defined HLA barriers in vitro. We demonstrate a synergistic effect when cells from the same biologic system were combined. This cell contact-independent function underlines the potential of clinical systemic application of MSCs.

Adipose‐derived stem cells integrate into trabecular meshwork with glaucoma treatment potential

“…There were no inflammatory cells at 2 weeks after stem cell transplantation, but inflammatory cells persisted in the corneas with fibroblast injection. ADSCs have effective immunomodulation characteristics, 70 which may have been partially lost in differentiated ADSC‐TM cells and which might explain why ADSC‐TM cells had higher inflammatory and immune responses than ADSCs. Further studies are needed to explore this phenomenon.…”

Immunomodulatory Effect of Adipose-Derived Stem Cells: The Cutting Edge of Clinical Application

“…The immunosuppressive ability of ASCs is both dose and cell passage dependent (Waldner et al, 2018). After the isolation of ASCs from adipose tissues, these cells undergo multiple culture passages in vitro, since significant numbers are needed for autologous clinical applications.…”

Differences in the Inflammatory Response of White Adipose Tissue and Adipose-Derived Stem Cells

“…Human white fat cells and stem cells, derived of white fat tissue (ADSCs), have been shown to exert immunomodulatory effects both in vitro and in vivo [6][7][8]. White adipose tissue (WAT) is a highly complex organ.…”

“…ADSCs can exert immunomodulation through direct contact with immune cells or by secretion of paracrine factors [5,7,8]. Dependent on their microenvironment, ADSCs exhibit pro-inflammatory and anti-inflammatory properties [6]. ADSCs have the ability to interact with many components of the innate immune system, including soluble complement, macrophages, dendritic cells, neutrophils, mast cells and natural killer cells [6,25,26].…”

“…Dependent on their microenvironment, ADSCs exhibit pro-inflammatory and anti-inflammatory properties [6]. ADSCs have the ability to interact with many components of the innate immune system, including soluble complement, macrophages, dendritic cells, neutrophils, mast cells and natural killer cells [6,25,26]. Furthermore, ADSCs have the capacity to interfere with the adaptive immune system [27][28][29].…”