What Holds Skin Together?


A study by the Spanish National Cancer Research Centre (CNIO) has demonstrated that interactions between skin stem cells maintain the architecture of skin. Skin stem cells are responsible for the constant renewal of the skin, and without the close connections between these cells, skin is unable to protect our bodies from the constant assaults from bacteria, chemicals, ultraviolet radiation, heat, cold, shear forces and so on.

A loss of proper adhesion between skin cells sometimes occurs during particular inflammatory diseases and cancer as well. This simple fact has stimulated interest in skin research.

Mirna Pérez-Moreno, who heads the Epithelial Cellular Biology Group that led this study, said, “We knew that these junctions [between skin stem cells] were important in skin stem cells but the cellular components involved in their structure and function were not yet understood.”

For this research, Pérez-Moreno and her team used skin stem cells from laboratory mice. They examined structures called “adherens junctions” between stem cells. Adherens junctions are found at the “apical” (or top) surface of the cells, and they hold cells together. Without adherens junctions, cells would fail to stick together properly.

Adherens junctionCellJunctions

Pérez-Moreno and her team discovered that one of the central structures in skin stem cells that stabilized adherens junctions were microtubules. Microtubules are stiff, tube-like structures that act as rebar-like reinforcement for cells and help cells maintain their shape, form, and structure.

microtubulemicrotubulesfigure2

Marta Shahbazi, a member of Pérez-Moreno’s research group, said,” We have seen for the first time that skin stem cell microtubules connect with cell-cell junctions to form velcro-like structures that hold the cells together.”

The microtubules and the adherens junctions are stuck together by means an interaction between two proteins, the CLASP2 and p120 catenin proteins.

“We found that the absence of CLASP2 or p120 catenin in epidermal stem cells caused a loss of their adhesion , and therefore the structure of these cells,” said Shahbazi.

“Our results will open up new paths for exploring how these proteins regulate skin physiology,” said Perez-Moreno. She also added that such knowledge will be important for the possible development of future regenerative medical treatments or anti-cancer treatments.

Improving Cartilage Production By Stem Cells


To repair cartilage, surgeons typically take a piece of cartilage from another part of the injured joint and patch the damaged area, this procedure depends on damaging otherwise healthy cartilage. Also, such autotransplantation procedures are little protection against age-dependent cartilage degeneration.

There must be a better way. Bioengineers want to discover more innovative ways to grow cartilage from patient’s own stem cells. A new study from the University of Pennsylvania might make such a wish come true.

This research, comes from the laboratories of Associate professors Jason Burdick and Robert Mauck.

“The broad picture is trying to develop new therapies to replace cartilage tissue, starting with focal defects – things like sports injuries – and then hopefully moving toward surface replacement for cartilage degradation that comes with aging. Here, we’re trying to figure the right environment for adult stem cells to produce the best cartilage,” said Burdick.

Why use stem cells to make cartilage? Mauck explained, “As we age, the health and vitality of cartilage cells declines so the efficacy of any repair with adult chondrocytes is actually quite low. Stem cells, which retain this vital capacity, are therefore ideal.”

Burdick and his colleagues have long studied mesenchymal stem cells (MSCs), a type of adult stem cell found in bone marrow and many other tissues as well that can differentiate into bone, cartilage and fat. Burdick’s laboratory has been investigating the microenvironmental signals that direct MSCs to differentiate into chondrocytes (cartilage-making cells).

chondrocytes
chondrocytes

A recent paper from Burdick’s group investigated the right conditions for inducing fat cell or bone cell differentiation of MSCs while encapsulated in hydrogels, which are polymer networks that simulate some of the environmental conditions as which stem cells naturally grow (see Guvendiren M, Burdick JA. Curr Opin Biotechnol. 2013 Mar 29. pii: S0958-1669(13)00066-9. doi: 10.1016/j.copbio.2013.03.009). The first step in growing new cartilage is initiating cartilage production or chondrogenesis. To do this, you must convince the MSCs to differentiate into chondrocytes, the cells that make cartilage. Chondrocytes secrete the spongy matrix of collagen and acidic sugars that cushion joints. One challenge in promoting MSC differentiation into chondrocytes is that chondrocyte density in adult tissue is rather low. However, cartilage production requires that the chondrocytes be in rather close proximity.

Burdick explained: “In typical hydrogels used in cartilage tissue engineering, we’re spacing cells apart so they’re losing that initial signal and interaction. That’s when we started thinking about cadherins, which are molecules that these cells used to interact with each other, particularly at the point they first become chondrocytes.”

Desmosomes can be visualized as rivets through the plasma membrane of adjacent cells. Intermediate filaments composed of keratin or desmin are attached to membrane-associated attachment proteins that form a dense plaque on the cytoplasmic face of the membrane. Cadherin molecules form the actual anchor by attaching to the cytoplasmic plaque, extending through the membrane and binding strongly to cadherins coming through the membrane of the adjacent cell.
Desmosomes can be visualized as rivets through the plasma membrane of adjacent cells. Intermediate filaments composed of keratin or desmin are attached to membrane-associated attachment proteins that form a dense plaque on the cytoplasmic face of the membrane. Cadherin molecules form the actual anchor by attaching to the cytoplasmic plaque, extending through the membrane and binding strongly to cadherins coming through the membrane of the adjacent cell.

In order to simulate this microenvironment, Burdick and his collaborators and colleagues used a peptide sequence that mimics these cadherin interactions and bound them to the hydrogels that were then used to encapsulate the MSCs.

According to Mauck, “While the direct link between cadherins and chondrogenesis is not completely understood, what’s known is that if you enhance these interactions early during tissue formation, you can make more cartilage, and, if you block them, you get very poor cartilage formation. What this gel does is trick the cells into think it’s got friends nearby.”

See L Bian, et al., PNAS 2013; DOI:10.1073/pnas.1214100110.