Compositions and methods for restoring or rejuvenating stem/progenitor cell function
This invention relates to the use of autologous stem/progenitor cells to restore or rejuvenate adult stem cell function in a mammal, wherein the restoration or rejuvenating extends lifespan and/or improves health of the mammal. In addition, the invention also relates to compositions containing one or more regulatory factors secreted or released from isolated mammalian stem/progenitor cells and use of such compositions to extend lifespan and/or improve health of a mammal. Also provided are methods of treating, delaying, preventing or reversing progeria or related syndromes in a mammal using isolated autologous or allogeneic stem/progenitor cells and/or regulatory factors secreted or released therefrom.
1. A method of restoring or rejuvenating function of adult muscle-derived stem/progenitor cells (MDSPCs) having cell proliferation and/or differentiation defects, comprising:
exposing said adult MDSPCs to an exogenous amount of isolated young allogeneic MDSPCs and an inhibitor of mTOR and/or of IKK/NF-κB pathway, wherein said isolated allogeneic MDSPCs secrete or release one or more regulatory factors comprising RBP-JK inhibitory factor, Stanniocalcin-1, Wnt3a, KLOTHO, CCL11, miRNA-489, VEGF, HGF, IGF, and Her-2/neu (ERBB2/c-erbB-2);
wherein said one or more secreted or released regulatory factors restore or rejuvenate said adult MDSPCs function.
2. The method of claim 1 , wherein the adult MDSPCs are from a mammal carrying a xeroderma pigmento sum complement group F mutation.
3. A method of treating, delaying, or reversing effects due to activation of ROS in adult muscle-derived stem/progenitor cells (MDSPCs), comprising contacting said adult MDSPCs with an effective amount of isolated young allogeneic MDSPCs and an inhibitor of mTOR, wherein said isolated young allogeneic MDSPCs secrete or release one or more regulatory factors comprising RBP-JK inhibitory factor, Stanniocalcin-1, Wnt3a, KLOTHO, CCL11, miRNA-489, VEGF, HGF, IGF, and Her-2/neu (ERBB2/c-erbB-2);
wherein said one or more secreted or released regulatory factors treat, delay, or reverse one or more effects due to activation of ROS pathway of said adult MDSPCs.
4. The method of claim 1 , wherein the inhibitor of IKK/NF-κB pathway is a Nemo Binding Domain (8K-NBD) peptide.
5. The method of claim 3 , wherein the inhibitor of mTOR is rapamycin.
6. The method of claim 1 , wherein the inhibitor of mTOR is rapamycin.
7. The method of claim 3 , wherein said adult MDSPCs has a xeroderma pigmentosum complement group F mutation.
8. The method of claim 1 or 3 , wherein said adult MDSPCs has a mutation in excision repair cross-complementation group-1.