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Dedifferentiated, programmable stem cells of monocytic origin, and their production and use

Patent Number: 7,138,275

Date of First Priority Issue: Thursday March 28th, 2002
Date Issued: Tuesday November 21st, 2006
Assignee: Blasticon Biotechnologische Forschung GmbH (Keil, DE)
Inventors: Kremer; Bernd Karl Friedrich (Kiel, DE), Fandrich; Fred (Kiel, DE), Ruhnke; Maren ne (Kiel, DE)

From Class: Type

This patent is highly interesting in that the inventors claim to have devised a simple and easy to implement methodology for generation of autologous stem cells. Essentially, the invention teaches that culturing of peripheral blood monocytes in the presence of IL-3 and M-CSF for approximately 6 days, somehow induces a program of de-differentiation in the monocytes to endow them with stem cell like potential. The patent goes on to demonstrate that these monocytes can be converted into islets, hepatocytes, and neural cells. In vivo experiments include hepatic regeneration with monocyte derived stem cells, as well as inducing insulin independence in streptozocin-treated diabetic mice..

This patent has 9 independent claims.

The first covers a cell type that originates from the monocytic lineage, once dedifferentiated is programmable, and expresses CD14, CD90, and CD123.

The second covers essentially the same as the first with the exception that the phenotype is CD14+, CD90+ and CD135+

The third covers essentially the same thing as the first, with the exception that the antigen CD135 is added.

The forth covers a pharmaceutical composition derived from the programmable dedifferentiated cells of monocytic origin, the cell expressing the markers CD14 and CD90.

The fifth covers essentially the same as the forth with the exception that the CD123 antigen is added as a marker.

The sixth covers essentially the same as the fifth with the exception that the CD135 antigen is added as a marker.

The seventh covers essentially the same as the first except that only CD14 and CD90 are claimed as antigens.

The eighth covers the cell with CD14 and CD90, but having ability to differentiate into a cell that is selected from a group comprising of neurons, endothelial cells, adipocytes, hepatocytes, keratinocytes, and insulin-producing cells.

The ninth covers essentially the same as the eighth except the cell is able to differentiate into a cell selected from: glia cells, neurons, neuronal precursor cells, endothelial cells, adipocytes, hepatocytes, keratinocytes, and insulin-producing cells.

Dependent claims cover transfection of the cells with genes, as well as growth of the cells in liquid media.

This patent appears very promising for commercialization. Additionally, scientific replication of these experiments is bound to provide a wealth of new papers as well as novel methods of improving on this technology.

One possible combination of technologies would be to link this patent with the teachings of US patent #6897060 which teaches use of neural cells for stimulation of hematopoiesis.

View this patent on the USPTO website.

Added to StemCellPatents.com on Sunday November 26th, 2006

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8 Comments | Add Comment

Stan said...

Created 2006-11-29 19:30:58 EST

I dont belief that monocytes become dedifferentiated. The authors have not published this work. As far as I am concerned they are just looking at Dendritic Cells !!!

- 1 -

notch1 said...

Created 2006-11-30 19:25:14 EST

delirium!!!
no point to talk about stem cells here and so-called "de- re- differentiation"

- 2 -

SSlavin said...

Created 2006-12-01 12:27:49 EST

I dont know if its "delirium", did you see the paper "Abuljadayel IS. Induction of stem cell-like plasticity in mononuclear cells derived from unmobilised adult human peripheral blood. Curr Med Res Opin. 2003;19(5):355-75." ??

There is also a news clip about this paper.

Also a patent

- 3 -

notch1 said...

Created 2006-12-01 23:06:11 EST

yes i did when it was published 3 years ago, i'm watching everything around TriStem...
so what? I think that paper was published only because of hot topic and what journal? Who read this journal from stem cell world?
It was definitely publication only for publish something ASAP...

firstly authors can not use term "stem cell" while they didn't show self-renewal ability of discribed population in serial transplant experiment,
secondly, authors can not use "transdifferentiation" term based only on morphology and cell surface phenotype (markers expression), it's required to show function of them in vivo + exclude fusion phenomen

business is business, science is science

- 4 -

SSlavin said...

Created 2006-12-02 12:13:55 EST

I tend to agree, but did u see that they recently reported using these cells clinically?

Wouldnt it be nice if outside in signalling could be a magic wand and dedifferentiate cells into stem cells?

LEt me ask you notch1, what do u think is the best way to generate stem cells from adults...if any...

- 5 -

notch1 said...

Created 2006-12-03 22:29:45 EST

i didn't see any clinical paper of them,
can you give us a link?
yes i agree it could be very nice to reprogramm adult cells to real stem cells,
but so far i don't know any proven method for human cells which allow to get real stem cells.
It's really nice concept but still magic and elusive.
And i think we have enough sources of SC in adult human body - HSC and mesenchymal stromal SC,
we can mobilize them to periphery, we have cord blood,
all of SC from those sources usually god enough for cell therapy of plenty diseases

so i think the best way do not generate them but just take them off, if it's neccessery do something magic ex vivo and transplant them back
and progenitors are preference but not pluripotential SC with expression ES markers

but it's separate discussion
off topic here

- 6 -

Sslavin said...

Created 2006-12-04 00:28:22 EST

Here is the paper reference....


*Abuljadayel IS, Quereshi H, Ahsan T, Rizvi S, Ahmed T, Khan SM, Akhtar J, Dhoot G. Related
Infusion of autologous retrodifferentiated stem cells into patients with beta-thalassemia.
ScientificWorldJournal. 2006 Oct 9;6:1278-97.*

u will notice the stunning caliber of the journal it is published in ;)

- 7 -

Paul Nagourney said...

Created 2007-01-16 13:50:07 EST

Doesnt this predate Opexa's 20050003534 application that they paid $1.5 million???

- 8 -

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