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Molly Stevens: A new way to grow bone - YouTube

What does it take to regrow bone in mass quantities? Typical bone regeneration — wherein bone is taken from a patient's hip and grafted onto damaged bone els...
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Molly stevens talks about bone regeneration in TED.

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A combinatorial cell-laden gel microarray for inducing osteogenic differentiation of human mesenchymal stem cells : Scientific Reports

A combinatorial cell-laden gel microarray for inducing osteogenic differentiation of human mesenchymal stem cells : Scientific Reports | Stem Cells & Tissue Engineering | Scoop.it
Jacob Blumenthal's insight:

In this open-access paper, the authors describe a novel method of screening for  microenvironments that direct  osteogenic differentiation of mesenchymal stem cells. 

http://www.nature.com/srep/2014/140129/srep03896/full/srep03896.html


Learn more about mesenchymal stem cells:

http://discovery.lifemapsc.com/in-vivo-development/mesenchymal-stem-cells

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iPSCs used to model disease causing abnormal bone growth | Stem Cells Freak

iPSCs used to model disease causing abnormal bone growth | Stem Cells Freak | Stem Cells & Tissue Engineering | Scoop.it
Researchers use induced pluripotent stem cells to model Fibrodysplasia ossificans progressiva.
Jacob Blumenthal's insight:

Researchers from Researchers from the University of California - San Francisco developed an induced pluripotent stem cell (iPSC) line from  fibrodysplasia ossificans progressiva (FOP) patient. In this rare disease, muscles and tendons progressively turn into bone. When differentiated into bone tissue, FOP iPS cells exhibited an increase in mineralization and enhanced chondrogenesis in vitro. 

 

To read the full article: http://www.ojrd.com/content/8/1/190

 

Learn about bone development: http://discovery.lifemapsc.com/in-vivo-development/bone


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Novel Col2a1-EGFP iPS Cells used to monitor chondrogenic differentiation

Novel Col2a1-EGFP iPS Cells used to monitor chondrogenic differentiation | Stem Cells & Tissue Engineering | Scoop.it
Jacob Blumenthal's insight:

In this open-access paper, Saito et al. generated induced pluripotent stem cells (iPSC) from embryonic fibroblasts of Col2a1-GFP transgenic mice, by transducing them with a viral cocktail of the iPSC factor genes Klf4, Sox2, Oct4, and c-Myc. The resulting iPSCs were...(click the picture)

 

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Cell Stem Cell - Stem Cells in the Face: Tooth Regeneration and Beyond

Cell Stem Cell - Stem Cells in the Face: Tooth Regeneration and Beyond | Stem Cells & Tissue Engineering | Scoop.it

Summary: "The face distinguishes one person from another. Postnatal orofacial tissues harbor rare cells that exhibit stem cell properties. Despite unmet clinical needs for reconstruction of tissues lost in congenital anomalies, infections, trauma, or tumor resection, how orofacial stem/progenitor cells contribute to tissue development, pathogenesis, and regeneration is largely obscure. This perspective article critically analyzes the current status of our understanding of orofacial stem/progenitor cells, identifies gaps in our knowledge, and highlights pathways for the development of regenerative therapies".

Jacob Blumenthal's insight:

This is a free review from Cell Stem Cell describing stem cells in the face. It was first published in September 2012, and is now available as part of the Featured Five review collection.

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To learn more about the embryonic development of the head mesenchyme and the bones:

http://discovery.lifemapsc.com/in-vivo-development/head-mesenchyme

http://discovery.lifemapsc.com/in-vivo-development/bone

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For stem cells differentiation protocols:

http://discovery.lifemapsc.com/stem-cell-differentiation/protocols

 

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How 3D Printing Can Build New Bone

How 3D Printing Can Build New Bone | Stem Cells & Tissue Engineering | Scoop.it
Members of the public can try the new method themselves at the Royal Society’s Summer Science Exhibition.
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Engineering bone tissue using human Embryonic Stem Cells

Bone defects lead by traumatic injuries, congenital malformations and other surgical rescissions rises the immediate need for a more evolved and safer approa...
Jacob Blumenthal's insight:

This is a nice presentation on the use of human embryonic stem cells for tissue engineering of bone tissue.

Find more protocols here: http://discovery.lifemapsc.com/stem-cell-differentiation/protocols?treeFilter=CB81592A-120B-4419-82A8-AE10AAB3478D

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Bioactive Scaffolds for the Controlled Formation of Complex Skeletal Tissues | InTechOpen

Bioactive Scaffolds for the Controlled Formation of Complex Skeletal Tissues | InTechOpen, Published on: 2011-08-29. Authors: Sandra Hofmann and Marcos Garcia-Fuentes
Jacob Blumenthal's insight:

This is an open-access book chapter entitled "Bioactive Scaffolds for the Controlled Formation of Complex Skeletal Tissues".

Also check the regenerative medicine and tissue engineering book collection:

http://www.intechopen.com/subjects/tissue-engineering-and-regenerative-medicine

 

 

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Christopher Duntsch's curator insight, January 23, 2014 3:21 AM

This is a good review and report of what is trending now in tissue engineering. The push early was therapies with cells derived from mature tissue, or tissue sections from mature tissues, that were transferred into a degenerated, damaged, or diseased tissue with the hope of some sort of therapeutic or regenerative healing or reversal of the disease process. There are a few exceptions, but this approach never worked well in vitro, in vivo in animals, much less in the clinical studies that followed. The shift to stem cell technologies was a paradigm shift and in the right direction, but still there has not been a great deal of success using stem cell therapies in isolation. There are rare exceptions as always (HSCs and BM transplants).

 

Years ago and even more so recently, the definition of tissue engineering, has changed significantly. There are now so called core components, and is agreed by most that the ‘sum of the parts are greater than the "whole". In the most basic sense, I would think it could be simplified to 1) a stem cell product or therapeutic 2) support factors of many types … growth factors, nutrients, supplements, etc., 3) a 3D scaffold of some type.

 

This article keys in on successes that have begun to be seen in the scientific literature as of late. Namely, that in addition to the above, one must consider the impact of stem cells as before, but also of progenitor cells, changes in phenotype that are smart and strategic and also in line with fundamental biology, and for lack of a better word for it, developmental biology.  In any normal solid organ, there is a rare but immortal adult stem cell population, and that stem cell is quiescent most often, at least in a healthy state. However, inflammation and other molecular events that occur with disease and damage and degeneration can push quiescent stem cells to asymmetrically give off early progenitors. These are the machines of tissue development, as they are of effective regenerative medicine.

 

As early progenitors mature, they change in phenotype, lose stem cell phenotypy, and gain terminal lineage phenotypy. Eventually, as cells proliferate and migrate and fill a tissue niche, they crowd and mature and secrete ECM and enzymes.  EC enzymes such as MMPs, and Cell surface adhesion molecules and receptors, interact with ECM such as proteoglycans and glycosaminoglycans, and eventually cells fix in space in time, communicate locally, and organize. The result is prefabricated tissue that is the infrastructure and architectural pathway to the end goal.. As this remodels continuously, the cell and tissue and the structure / architecture remodels and continues to mature and evolve.  Ideally, a relatively regenerated tissue with structure, order, and function, is left where once there was damaged or nonfunctional tissue.

 

The point of the above is that the rough approximation of developmental biology in vitro in not just important but required  for successful tissue engineering. And this requires more than the three core components mentioned. Without more detail, it is enough to simply make these descriptive comments. Despite the lack of detail for what follows, it is fairly logical to assume that an in vitro developmental biology influence is indeed a key fourth core for tissue engineering.

 

Principles of Tissue Engineering with the following four core components.

1 A stem cell that is a proven therapeutic for the treated condition.

2 A supportive mix of growth factors, small molecules, media, glucose, ECM, as indicated.

3 A synthetic or organic but biocompatible 3D scaffold, and;

4 A series of key steps, protocols, manipulations that provide a  developmental nature or influence to the biological device prior to transplant into the animal.

 

In summary, a definition of an ideal tissue engineering product: A stem cell therapeutic, seeded into a tissue engineering complex in vitro, supplemented with ECM, GFs, supplements, etc, which, after methods and protocols are carried forward correctly, results in a comprehensive biological device or structure that has the following components:

1 a retained stem cell fraction with a phenotypically correct phenotype,

2 an early progenitor fraction rapidly dividing and migrating throughout the structure, and,

3  a small late progenitor fraction that is beginning to some degree to mature to the lineage of the cells needed for the tissue treated.

 

The importance is that the biological device used for tissue engineering is: primed genetically, epigenetically, and with respect to its cell and molecular phenotype; phenotypically more effective at integrating / assimilating into the target tissue, and immediately starts to grow, mature, change, and regenerate the tissue defect or replace / treat / supplement a diseased or degenerated tissue. Makes sense.

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Mimicking Developmental Chondrogenesis to Generate Chondrocytes In-Vitro

Mimicking Developmental Chondrogenesis to Generate Chondrocytes In-Vitro | Stem Cells & Tissue Engineering | Scoop.it
Jacob Blumenthal's insight:

Cartilage injury and lack of cartilage regeneration often lead to osteoarthritis, which involves degradation of joint components, including articular cartilage and subchondral bone. In a new open-access paper published in Stem Cell Reports, the authors explored the developmental cues governing articular cartilage geneartion in-vivo. They followed the developmental progression of primordial mesenchymal cells towards...(click on the image/link to read the full story).

http://us4.campaign-archive1.com/?u=985051700e9649000fa0c0d4a&id=77ce89ebff&e=aeb607fc5e

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Cell Stem Cell - Regional Localization within the Bone Marrow Influences the Functional Capacity of Human HSCs

Cell Stem Cell - Regional Localization within the Bone Marrow Influences the Functional Capacity of Human HSCs | Stem Cells & Tissue Engineering | Scoop.it
Jacob Blumenthal's insight:

Researchers from McMaster university, Canada published a paper in Cell Stem Cell journal, discussing the regional localization of hematopoietic stem cells (HSCs) withing the bone marrow. They found that HSC tend to localize to endosteal regions of the trabecular bone area (TBA). These cells have superior regenerative and self-renewal capacity and are molecularly distinct from those localizing to the long bone area (LBA).

This important paper, reveals that bone marrow localization is important to define the functional propeties of HSCs.

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TGF-β-releasing scaffolds for cartilage tissue engineering | Tissue Engineering Part B: Reviews

Jacob Blumenthal's insight:

Abstract: "The maintenance of a critical threshold concentration of TGF-β for a given period of time is crucial for the onset and maintenance of chondrogenesis. Thus, the development of scaffolds that provide temporal and/or spatial control of TGF-β bioavailability has appeal as a mechanism to induce the chondrogenesis of stem cells in vitro and in vivo for articular cartilage repair. In the past decade, many types of scaffolds have been designed to advance this goal: hydrogels based on polysaccharides, hyaluronic acid, alginate; protein-based hydrogels such as fibrin, gelatin, collagens; biopolymeric gels and synthetic polymers; and solid and hybrid composite (hydrogel/solid) scaffolds. Here, we review the progress in developing strategies to deliver TGF-β from scaffolds with the aim of enhancing chondrogenesis. In the future, such scaffolds could prove critical for tissue engineering cartilage, both in vitro and in vivo".

-----------------Commercial Section-------------------

To learn more about chondrogenic differentiation products:

http://bioreagents.lifemapsc.com/collections/differentiation-kits

http://bioreagents.lifemapsc.com/collections/purestem-packages

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NYSCF scientists create personalized bone substitutes from skin cells ... - EurekAlert (press release)

Daily Mail
NYSCF scientists create personalized bone substitutes from skin cells ...
Jacob Blumenthal's insight:

The researchers team generated bone constructs from iPS cells, characterized them in-vitro and transplanted them into animal models to examine their functionality, in-vivo.

 

Link: http://www.pnas.org/content/early/2013/05/07/1301190110

 

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Carlos Garcia Pando's curator insight, May 8, 2013 2:31 AM

http://www.nyscf.org/news/nyscf-in-the-news/item/1525-nyscf-scientists-create-human-bone-from-skin-cells

In a step towards personalized bone grafts to treat traumatic injury or congenital defects, a study, led by Darja Marolt, PhD, and Giuseppe Maria de Peppo, PhD, and published in the Proceedings of the National Academy of Sciences, reports the generation of patient-specific bone substitutes from skin cells for repair of large bone defects. This advance will facilitate the development of customizable, three-dimensional bone grafts on-demand, matched to fit the exact needs and immune profile of a patient. Taking skin cells, the NYSCF scientists utilized an advanced technique called “reprogramming” to revert adult cells into an embryonic-like state. The researchers differentiated the resultant induced pluripotent stem (iPS) cells into bone-forming progenitors and then seeded these cells onto a three-dimensional scaffold, which was placed into an artificial, biologically active environment, a bioreactor. Analysis revealed that, even in vitro, bone formed; and, when implanted in mice, the bone matured into typical dense, mineral-rich tissue. Next steps for this proof-of-concept research include protocol optimization and long-term safety trials in animal models.

 

This is the press release from NYSCF Read a press release on this research