Neonatal stem cells exhibit specific characteristics in function, proliferation, and cellular signaling that distinguish them from their adult counterparts.
Stem cells may be a novel treatment modality for organ ischemia, possibly through beneficial paracrine mechanisms. Stem cells from older hosts have been shown to exhibit decreased function during stress. We therefore hypothesized that 1) neonatal bone marrow mesenchymal stem cells (nBMSCs) would produce different levels of IL-6, VEGF, and IGF-1 compared with adults (aBMSCs) when stimulated with TNF or LPS; 2) differences in cytokines would be due to distinct cellular characteristics, such as proliferation or pluripotent potential; and 3) differences in cytokines would be associated with differences in p38 MAPK and ERK signaling within nBMSCs. BMSCs were isolated from adult and neonatal mice. Cells were exposed to TNF or LPS with or without p38 or ERK inhibition. Growth factors were measured via ELISA, proliferation via daily cell counts, cell surface markers via flow cytometry, and pluripotent potential via alkaline phosphatase activity. nBMSCs produced lower levels of IL-6 and VEGF, but higher levels of IGF-1 under basal conditions, as well as after stimulation with TNF, but not LPS. Neonatal and adult BMSCs had similar pluripotent potentials and cell surface markers, but nBMSCs proliferated faster. Furthermore, p38 and ERK appeared to play a more substantial role in nBMSC cytokine and growth factor production. Neonatal stem cells may aid in decreasing the local inflammatory response during ischemia, and could possibly be expanded more rapidly than adult cells prior to therapeutic use.
Markel
Troy A
TA
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
Wang
Meijing
M
Crisostomo
Paul R
PR
Manukyan
Maiuxi C
MC
Poynter
Jeffrey A
JA
Meldrum
Daniel R
DR
D053687:Adult Stem Cells / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001854:Bone Marrow Cells / Q000502:physiology; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D048069:Tumor Necrosis Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis
D015850:Interleukin-6; D008565:Membrane Proteins; D048069:Tumor Necrosis Factors; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases