Cartilage from stem cells: a new recipe
Hydrogel with peptide makes it possible to improve the production of cartilage from stem cells
Nanonews Network based on Penn News: Penn Research Shows Way to Improve Stem Cells’ Cartage FormationThe restoration of injured cartilage is a difficult task for medicine.
Surgical techniques used today are usually reduced to applying a "patch" – a section of cartilage taken from an intact part of the joint – to its injured part. This approach involves damage to healthy cartilage, not to mention the problem of permanent age-related deterioration of cartilage tissue, which is absolutely not solved by it.
Bioengineers are actively looking for innovative ways to grow new cartilage from the patient's own stem cells, and, thanks to a new study by University of Pennsylvania scientists published in the journal Proceedings of the National Academy of Sciences (Bian et al., Hydrogels that mimic developmentally relevant matrix and N-cadherin interactions enhance MSC chondrogenesis), this method of treatment has become a step closer to clinical practice.
"We are trying to develop new methods of treatment for cartilage replacement, starting with focal defects – for example, sports injuries – and we hope that later we will be able to move on to replacing articular surfaces with age-related cartilage destruction. Now we are trying to find the right environment for adult stem cells that allows us to get the best cartilage," says Associate Professor Jason Burdick, PhD, head of the study.
"As we age, the viability of cartilage cells decreases, and the efficiency of its recovery due to adult chondrocytes is actually quite low. Therefore, the ideal in this case would be the use of stem cells that maintain high viability," adds Burdick's co–author associate Professor Robert Mauck, PhD.
Dr. Burdick and his colleagues have been studying mesenchymal stem cells for a long time – a type of adult stem cells located in the bone marrow that can differentiate into cells of bone, adipose and cartilage tissue. Scientists pay special attention to decoding the signals of the microenvironment that determine in which direction the differentiation of stem cells will go. In a recent study, they studied the conditions mediating their predominant transformation into fat or bone cells. Stem cells were encapsulated in hydrogels, polymer networks that mimic some of the conditions of the natural microenvironment in which cell growth occurs.
The first step in growing new cartilage is the initiation of chondrogenesis: scientists should be able to "convince" mesenchymal stem cells to differentiate into chondrocytes, which, in turn, form a spongy matrix of collagen and sugars – a "cushioning cushion" of joints. One of the problems with the direction of differentiation towards chondrocytes is due to the fact that, despite the low density of adult chondrocytes in tissues, the active formation of cartilage begins with cells located in close proximity to each other.
"In typical hydrogels used in cartilage tissue engineering," Dr. Burdick continues, "cells are located separately and therefore lose this initial signal and the corresponding interaction. That's when we thought about cadherins, the molecules used by these cells to interact with each other, especially at the first stage of their differentiation into chondrocytes."
To simulate such an active medium, scientists used a peptide sequence that mimics the properties of cadherins, linking it with hydrogels used to encapsulate mesenchymal stem cells.
"Although the direct link between cadherins and chondrogenesis is not entirely clear, it is known that if you manage to strengthen these interactions in the early stages of tissue formation, you can get more cartilage, and if you block them, the formation of cartilage is suppressed. Such a gel deceives the cell, making it think that friends are nearby," explains Dr. Mock.
Fluorescent protein-labeled mesenchymal stem cells
in a hydrogel with hyaluronic acid (photo: Megan Farrell)
To test the effectiveness of their cadherin-mimicking peptides, scientists encapsulated mesenchymal stem cells in some other types of gels: a conventional hydrogel without peptides, a hydrogel with a non-functional variant of the peptide, and a hydrogel with both a peptide and an antibody blocking cadherin-mediated interactions.
After a week, the cells in the gel containing the cadherin-mimicking peptide showed more genetic markers of chondrogenesis than the cells that developed in any of the control variants of the gels.
The second experiment consisted in growing cells encapsulated in gels for four weeks – long enough for the formation of the cartilage matrix to begin. This allowed the researchers to conduct functional tests by subjecting the gels, in particular, to mechanical loads. Gels containing peptides showed properties closer to natural cartilage than control variants.
Staining of peptide–containing gels for type II collagen and chondroitin sulfate – the molecules that make up the cartilage matrix - also confirmed that peptide-containing gels produce more of these markers of matrix formation.
"Taken together, these experiments fully prove that the cadherin signal received by cells from a synthetic hydrogel enhances differentiation in the direction of chondrogenesis," concludes Dr. Burdick.
Portal "Eternal youth" http://vechnayamolodost.ru07.06.2013