Autologous point-of-care cellular therapies variably induce equine mesenchymal stem cell migration, proliferation and cytokine expression.
BACKGROUND
Autologous cellular therapy products including adipose-derived stromal vascular fraction (SVF), bone marrow mononuclear cells (BMMNs), cord blood mononuclear cells (CBMNs) and platelet rich plasma are options for treatment of acute orthopaedic lesions while mesenchymal stem cells (MSCs) are culture expanded. These products may contribute to healing by secreting matrix proteins or growth factors, but they may also act on endogenous MSCs to facilitate healing.


OBJECTIVE
To determine the effects of cell therapy products on MSCs function in vitro. The hypothesis was that cell therapy products promote MSCs functions including proliferation, migration and mediator release.


METHODS
Fat, bone marrow (BM), cord blood and platelets were obtained from 6 Quarter Horses. The BM-MSCs and their autologous cell therapy products were co-incubated in transwells. Mesenchymal stem cells proliferation, migration, gene expression and cytokine concentrations were determined.


RESULTS
All cell therapy products increased MSCs proliferation, but SVF induced significantly more proliferation than any other product. Also SVF elicited more MSCs chemotaxis and, along with BMMNs, significantly more MSCs chemoinvasion. Cord blood mononuclear cells stimulated MSCs to produce high concentrations of interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1), and prostaglandin E(2) (PGE(2)). Stromal vascular fraction and platelet lysate did not stimulate MSCs but SVF and platelet lysate themselves contained high concentrations of PGE(2) and IL-6 (SVF) and TGF-β1 (platelet lysate).


CONCLUSIONS
Autologous cell products variably stimulate MSCs functions with 2 primary patterns apparent. Products either contained preformed mediators that may have intrinsic healing function, or products stimulated MSCs to secrete mediators.


CONCLUSIONS
The specific clinical indications for these products may differ to include administration as a sole treatment modality prior to MSCs injection for intrinsic cell and cytokine activity (i.e. SVF) or administration concurrently with MSCs to activate MSCs for treatment of chronic lesions (i.e. CBMNs).
Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, USA.
A
A
Kol
N J
NJ
Walker
L D
LD
Galuppo
K C
KC
Clark
S
S
Buerchler
A
A
Bernanke
D L
DL
Borjesson
D000273:Adipose Tissue / Q000166:cytology / Q000502:physiology; D000818:Animals; D001792:Blood Platelets; D016026:Bone Marrow Transplantation / Q000379:methods; D018929:Cell Culture Techniques / Q000379:methods; D049109:Cell Proliferation; D002633:Chemotaxis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology; D005786:Gene Expression Regulation / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D019095:Point-of-Care Systems
D016207:Cytokines