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Method for stem cell differentiation in vivo by delivery of morphogenes with mesoporous silica and corresponding pharmceutical active ingredients

a technology of mesoporous silica and stem cell differentiation, which is applied in the field of stem cell differentiation in vivo by delivery of morphogenes with mesoporous silica and corresponding pharmceutical active ingredients, to achieve the effects of enhancing cell survival, improving initial survival of transplanted stem cells, and maintaining long-term viability

Inactive Publication Date: 2013-11-28
NANOLOGICA AB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a method for enhancing the survival of stem cells during implantation and promoting their differentiation into desired cell types. This may be useful for improving the initial survival of transplantable cells and maintaining their long-term viability. The invention involves the use of sonic hedgehog agonist purmorphamine and retinoic acid, which can be delivered to cells through the use of mesoporous nanoparticles. The invention also provides a method for promoting cardiac structural repair and functional restoration in animals models of myocardial injury by delivering stem cells through various routes such as intravascular or cardiac transplantation. The invention also discusses the reduced migration of stem cells and increased differentiation in the initial location when co-transplanted with another cell type.

Problems solved by technology

However, addition of multiple FGFs, BMP antagonists and Wnt antagonists to the chick embryonic epiblast is not sufficient to induce the expression of the neural marker Sox2, suggesting that still other pathways regulate neural induction (Linker C, Stern CD.

Method used

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  • Method for stem cell differentiation in vivo by delivery of morphogenes with mesoporous silica and corresponding pharmceutical active ingredients
  • Method for stem cell differentiation in vivo by delivery of morphogenes with mesoporous silica and corresponding pharmceutical active ingredients
  • Method for stem cell differentiation in vivo by delivery of morphogenes with mesoporous silica and corresponding pharmceutical active ingredients

Examples

Experimental program
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Effect test

example 1

Induced Differentiation of Transplanted Human Embryonic Stem Cells with Shh and Retinoic Acid Delivered with Mesoporous Silica

[0116]Background:

[0117]Embryonic stem cells (ESCs) differentiate into motor neurons, establish functional synapses with muscle fibers, and acquire physiological properties characteristic of embryonic motor neurons when cultured with sonic hedgehog (Shh) agonist and retinoic acid (RA) (Wichterle H, Lieberam I, Porter J A, et al. Directed differentiation of embryonic stem cells into motor neurons. Cell 2002; 110:385-97; Miles G B, Yohn D C, Wichterle H, et al. Functional properties of motoneurons derived from mouse embryonic stem cells. J Neurosci 2004; 24:7848-58). ESC-derived motorneurons transplanted into the developing chick neural tube projected axons toward muscles, received synaptic input, and developed electrophysiological properties similar to endogenous motor neurons (Soundararajan P, Miles G B, Rubin L L, et al. Motoneurons derived from embryonic ste...

example 2

Differentiation of Neural Crest Stem Cells Toward Neuronal Phenotype In Vitro by RA Delivered with Mesoporous Silica

[0129]Background:

[0130]The RA receptor RAR-beta2 is expressed in dorsal root ganglion (DRG) neuron subtypes. It was shown that retinoid signaling has a role in neurite outgrowth in vivo (Corcoran J, Shroot B, Pizzey J, et al. The role of retinoic acid receptors in neurite outgrowth from different populations of embryonic mouse dorsal root ganglia. J. Cell Sci 2000; 113:2567-74; Dmetrichuk J M, Spencer G E, Carlone R L. Retinoic acid-dependent attraction of adult spinal cord axons towards regenerating newt limb blastemas in vitro. Dev Biol 2005; 281:112-20) by demonstrating that in a peripheral nerve crush model there is less sensory neurite outgrowth in RAR-beta null compared to wild-type mice. In vitro experiments identified sonic hedgehog (Shh) as a downstream target of the RAR-beta2 signaling pathway since it is expressed in the injured DRG of wild-type but not RAR-...

example 3

Differentiation and Migration of NCSCs in the Presence of AMS Under the Kidney Capsule

[0145]Background:

[0146]We previously showed that NCSCs transplanted under the kidney capsule of one pole of the kidney extensively migrate towards co-transplanted pancreatic islets placed in the opposite pole of the same kidney (Olerud J, Kanaykina N, Vasylovska S, et al. Neural crest stem cells increase beta cell proliferation and improve islet function in co-transplanted murine pancreatic islets. Diabetologia 2009; 52:2594-601. Erratum in: Diabetologia. 2010; 53:396. Vasilovska, S [corrected to Vasylovska, S]; Kozlova E N, Jansson L. Differentiation and migration of neural crest stem cells are stimulated by pancreatic islets. Neuroreport 2009; 20:833-8). The purpose of these previous studies was to develop a new protocol for improved outcome after transplantation of pancreatic islets. Transplantation of pancreatic islets is an established therapy in selected patients with type 1 diabetes. The sur...

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Abstract

A pharmaceutical active ingredient for cell differentiation to alleviate cell and cell-related deficiencies in mammals comprising porous silica containing a releasable agent capable of contributing to a cell environment conducive for stem cell differentiation in co-implanted stem cells and / or in endogenous stem cells.

Description

FIELD OF THE INVENTION[0001]The present invention relates to pharmaceutical active ingredients comprising sets composed of stem cells and porous silica, preferably mesoporous silica, containing a defined set of differentiation factors for desired differentiation of different types of cells, and to a method of enhancing survival and control differentiation of transplanted stem cells for regenerative medicine by providing said sets. In particular, the pharmaceutical active ingredients and methods of the invention are preferably used for controlling differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs); in general, they are also applicable for other stem cells, e.g. tissue-specific stem cells and mesenchymal stem cells.BACKGROUND OF THE INVENTION[0002]Experimental stem cell research has achieved enormous progress during the past few years in generating desired types of cells in vitro, which can be used in regenerative medicine. These in vitro protoco...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K47/02A61K35/30A61K35/54A61K31/5377A61K31/203A61K35/545
CPCA61K47/02A61K31/5377A61K31/203A61K35/545A61K35/30A61K9/5115A61K31/00A61K38/185A61K38/1709C12N2501/385C12N2501/41C12N2533/14A61K9/1611C12N5/0619C12N2506/02A61P21/00A61P25/00A61K2300/00C12N2500/38C12N2500/46C12N2501/998C12N2506/08C12N2533/00
Inventor GARCIA-BENNETT, ALFONSO E.KOZLOVA, ELENA NICKOLAEVNA
Owner NANOLOGICA AB
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