HIGHLY SPECIFICITY OF EFFECTOR CELLS TO INDUCE DIFFERENT TYPE OF NEURAL PROGENITOR CELLS FROM AMSC

Abstract

Background & Aim

In 2006 it was published that lymphocytes, with autoimmune effector activity (EC), against the Central Nervous System (CNS) induce MSCs to differentiate into neural progenitor cells. Furthermore, both cell types combined were able to repair damage to the CNS. Subsequently, a similar phenomenon was found in the coincubation of EC against cartilage, bone, skeletal muscle, retina and recently in smooth muscle and urothelium on aMSC. In each case, MSCs became progenitor cells of the tissue against which ECs were activated. To study the degree of specificity of ECs with respect to their induction of cellular and tissue differentiation, the following experimental plan was proposed.

Methods, Results & Conclusion: Materials and methods

3 similar but different antigens (of porcine origin) were identified: whole brain extract, substantia nigra and autonomic splanchnic ganglion. Next, they challenged MNC from human blood (obtained through volunteer red cross donors) to obtain EC against these 3 different tissues. MNCs were incubated in bottles without attachment at concentration of 3.2 million per ml, in DMEM high glucose, enriched with 1% tissue antigen (Protein in micrograms). TC medium was enriched with famotidine (4.5 micrograms per ml) and indomethacin (10 micrograms per ml) to inhibit the growth of regulatory clones. Resulting ECs were cocultured with aMSCs of human origin (donated from lipoaspiration surpluses of aesthetic purposes) and placental stem cells (voluntarily donated by disease-free pregnant women at term). MSC differentiation was studied using tissue-specific differentiation markers.

Results

After three days, the three cocultures showed cells positive for tubulin 3 (universal marker of young neurons) and for GFAP (universal marker of Glia cells). Only cocultures where was used EC against Substantia Nigra showed positive cells for Tyrosine Hydroxylase (exclusive marker for Dopaminergic cells), and only cocultures that used EC for autonomic cells showed cells with marker TUJ1 and p75, markers for neurons and glia of the autonomic system.

Conclusion

The high specificity of ECs to induce the differentiation of various types of neurons leads us to think about a sophisticated form of epigenetic induction that accompanies the tissue-specific activation of effector cells.