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Prosaposin in the secretome of marrow stroma‐derived neural progenitor cells protects neural cells from apoptotic death
Author(s) -
Li Na,
Sarojini Harshini,
An Jin,
Wang Eugenia
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06565.x
Subject(s) - microbiology and biotechnology , biology , neural stem cell , progenitor cell , stromal cell , stem cell , apoptosis , programmed cell death , adult stem cell , cellular differentiation , cancer research , biochemistry , gene
J. Neurochem. (2010) 112 , 1527–1538. Abstract Functionally, adult stem cells not only participate in replication and differentiation to various cell lineages, but also may be involved in rescuing cells from apoptosis. Identifying functional factors secreted by stem cells, as well as their target cells, may advance our understanding of stem cells’ multifaceted physiologic functions. Here, we report that mouse bone marrow stromal cell‐derived neuroprogenitor cells (mMSC‐NPC) provide a protective function by secreting a key factor, prosaposin (PSAP), capable of rescuing mature neurons from apoptotic death. This factor is identified as the lead protein in the secretome of mMSC‐NPC cultures by tandem mass spectroscopic profiling, and further validated by western blotting and immunocytochemistry. The secretome of MSC‐NPC reduces toxin‐induced cell death in cultures of rat pheochromocytoma neuronal cells, human ReNcell CX neurons, and rat cortical primary neurons; removal of PSAP by immunodepletion annuls this protective effect. This neuronal protection against toxin treatment was validated further by the recombinant PSAP peptide. Interestingly, the secretome of neuronal culture does not possess such a self‐protective action. We suggest that upon injury, a subgroup of MSCs differentiates into neural/neuronal progenitor cells, and remains in this intermediate stem cell‐like stage, defending injured neighboring mature neurons from apoptosis by secreting PSAP.