Intestinal organoid captures interactions between stem cells and neighbouring Paneth cells (red).

Photo: Nalle Pentinmikko                    

Cellular interactions

Repairing aged tissue by messing with the neighbors

Researchers at the University of Helsinki have discovered how regenerative capacity of intestinal epithelium declines when we age.

Targeting of an enzyme that inhibits stem cell maintaining signaling rejuvenates the regenerative potential of an aged intestine. This finding may open ways to alleviate age-related gastrointestinal problems, reduce side-effects of cancer treatments, and reduce healthcare costs in the ageing society by promoting recovery. “This study highlights the importance of cellular interactions. Alterations inside one cell resulted in secretion of an aging factor that can be targeted with drugs, providing multiple attractive points for interventions”, says the principal investigator Pekka Katajisto, Associate Professor at the University of Helsinki and Karolinska Institutet.

The researchers published their findings in the journal Nature.

We were surprised to find that even young stem cells lost their capacity to renew tissue when placed next to old neighbors

Nalle Pentinmikko

The age-induced reduction in tissue renewal makes dosing of many common drugs challenging. Targeting of inhibitor called Notum may provide a new way to increase the therapeutic window and to promote recovery in societies with the aging population. Researchers believe that in addition to direct targeting of Notum, lifestyle factors such as diet may also provide means to reduce Notum, and thus improve tissue renewal and repair.

Using organoid culture methods, researchers understood that poor function of tissue repairing stem cells in old intestine was due to aberrant signals from the neighboring cells, known as Paneth cells. “Modern techniques allowed us to examine tissue maintenance at a single cell level, and revealed which cell types contribute to the decline in tissue function. We were surprised to find that even young stem cells lost their capacity to renew tissue when placed next to old neighbors”, says the lead author, PhD candidate Nalle Pentinmikko from the University of Helsinki.

Normally intestinal epithelium is renewed by stem cells that rely on activity of Wnt-signaling pathway. Surrounding cells produce molecules that activate this pathway. The study shows that during ageing, Paneth cells begin to express a secreted Wnt-inhibitor called Notum. Notum enzymatically inactivates Wnt-ligands in the stem cell niche, decreasing regenerative potential of intestinal stem cells. However, pharmacologic inhibition of Notum rejuvenated stem cell activity and promoted the recovery of old animals after treatment with a commonly used chemotherapeutic drug with severe side-effects in the gut.


Source: University of Helsinki

11.07.2019

Read all latest stories

Related articles

Photo

Bioengineering

Human heart tissue grown from stem cells improves drug testing

Researchers at the Institute of Bioengineering and Nanotechnology (IBN) of A*STAR have engineered a three-dimensional heart tissue from human stem cells to test the safety and efficacy of new drugs…

Photo

Cancer development

Tumor induction from a distance

Current view is that cancer development is initiated from cells that acquire initial DNA mutations. These in turn provoke additional defects, and ultimately the affected cells begin to proliferate in…

Photo

Stem cell research

3D bioprinting of cartilage could soon be a reality

A team of researchers at Sahlgrenska Academy has managed to generate cartilage tissue by printing stem cells using a 3D-bioprinter. The fact that the stem cells survived being printed in this manner…

Related products

Eppendorf – Mastercycler nexus X2

Research Use Only (RUO)

Eppendorf – Mastercycler nexus X2

Eppendorf AG
Sarstedt – Low DNA Binding Micro Tubes

Research Use Only (RUO)

Sarstedt – Low DNA Binding Micro Tubes

SARSTEDT AG & CO. KG
Shimadzu – CLAM-2030

Research Use Only (RUO)

Shimadzu – CLAM-2030

Shimadzu Europa GmbH