Bi-directional cell-pericellular matrix interactions direct stem cell fate

Ferreira, Sandra Reis; Motwani, Meghna S.; Faull, Peter; Seymour, Alexis J.; Yu, Tracy T. L.; Enayati, Marjan; Taheem, Dheraj K.; Salzlechner, Christoph; Haghighi, Tabasom; Kania, Ewa M.; Oommen, Oommen P.; Ahmed, Tarek; Loaiza, Sandra; Parzych, Katarzyna; Dazzi, Francesco; Varghese, Oommen P.; Festy, Frederic; Grigoriadis, Agamemnon E.; Auner, Holger W.; Snijders, Ambrosius P.; Bozec, Laurent; Gentleman, Eileen

doi:10.1038/s41467-018-06183-4

Cited by 103 publications

(109 citation statements)

References 73 publications

Supporting

Mentioning

104

Contrasting

Order By: Relevance

“…We first seeded 17IA4 cells on the surface of hydrogels and examined their attachment. In line with previous observations, cells do not adhere to MA‐HA hydrogels ( Figure A); however, 16 h after seeding, 17IA4 cells were adherent to MA‐HA‐Dopa hydrogels. HA has no sites for integrin‐mediated interactions, so cells do not attach to it, even in the presence of serum proteins.…”

supporting

confidence: 92%

“…Hyaluronic acid (HA) is a hydrophilic polysaccharide composed of repeating disaccharide units of N ‐acetylglucosamine and D‐glucuronic acid. HA possesses carboxyl and hydroxyl groups on its backbone suitable for chemical modification, allowing it to be cross‐linked to form hydrogels. Moreover, HA can be safely degraded by hyaluronidases, which are ubiquitous in vivo.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Adhesive Hydrogels for Maxillofacial Tissue Regeneration Using Minimally Invasive Procedures

Salzlechner

Haghighi

Huebscher

et al. 2020

Adv Healthcare Materials

Self Cite

View full text Add to dashboard Cite

Minimally invasive surgical procedures aiming to repair damaged maxillofacial tissues are hampered by its small, complex structures and difficult surgical access. Indeed, while arthroscopic procedures that deliver regenerative materials and/or cells are common in articulating joints such as the knee, there are currently no treatments that surgically place cells, regenerative factors or materials into maxillofacial tissues to foster bone, cartilage or muscle repair. Here, hyaluronic acid (HA)‐based hydrogels are developed, which are suitable for use in minimally invasive procedures, that can adhere to the surrounding tissue, and deliver cells and potentially drugs. By modifying HA with both methacrylate (MA) and 3,4‐dihydroxyphenylalanine (Dopa) groups using a completely aqueous synthesis route, it is shown that MA‐HA‐Dopa hydrogels can be applied under aqueous conditions, gel quickly using a standard surgical light, and adhere to tissue. Moreover, upon oxidation of the Dopa, human marrow stromal cells attach to hydrogels and survive when encapsulated within them. These observations show that when incorporated into HA‐based hydrogels, Dopa moieties can foster cell and tissue interactions, ensuring surgical placement and potentially enabling delivery/recruitment of regenerative cells. The findings suggest that MA‐HA‐Dopa hydrogels may find use in minimally invasive procedures to foster maxillofacial tissue repair.

show abstract

supporting

confidence: 92%

mentioning

confidence: 99%

Adhesive Hydrogels for Maxillofacial Tissue Regeneration Using Minimally Invasive Procedures

Salzlechner

Haghighi

Huebscher

et al. 2020

Adv Healthcare Materials

Self Cite

View full text Add to dashboard Cite

show abstract

“…This tight encapsulation within the hydrogel fibers allowed for efficient cell–cell and cell–matrix interactions (Figure 4b). Such interactions were previously shown to promote essential physiological processes, such as proliferation, differentiation, and maturation . On day 7, the cells have occupied the entire volume of the droplet and tightly packed, spread cells could be observed on the surface of the droplet (Figure 4c).…”

Section: Resultsmentioning

confidence: 66%

Injectable Cardiac Cell Microdroplets for Tissue Regeneration

Gal

Edri

Noor

et al. 2020

Small

View full text Add to dashboard Cite

One of the strategies for heart regeneration includes cell delivery to the defected heart. However, most of the injected cells do not form quick cell–cell or cell–matrix interactions, therefore, their ability to engraft at the desired site and improve heart function is poor. Here, the use of a microfluidic system is reported for generating personalized hydrogel‐based cellular microdroplets for cardiac cell delivery. To evaluate the system's limitations, a mathematical model of oxygen diffusion and consumption within the droplet is developed. Following, the microfluidic system's parameters are optimized and cardiac cells from neonatal rats or induced pluripotent stem cells are encapsulated. The morphology and cardiac specific markers are assessed and cell function within the droplets is analyzed. Finally, the cellular droplets are injected to mouse gastrocnemius muscle to validate cell retention, survival, and maturation within the host tissue. These results demonstrate the potential of this approach to generate personalized cellular microtissues, which can be injected to distinct regions in the body for treating damaged tissues.

show abstract

“…Exploratory data analysis and filtering: The data count matrix was filtered for genes with a mean of less than 3 to remove very low count genes, and genes where most of the counts were zero were also removed. Research Ethics Service to release human material for research (12/WA/0196) as previously described 48 . The samples for this project were issued from sub-collection R16052.…”

Section: Rnasequencing Data Analysismentioning

confidence: 99%

ILC1-derived TGFβ1 drives intestinal remodelling

Jowett

Norman

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we developed gut organoid co-cultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines.We demonstrate for the first time that murine and human ILC1 secrete TGFβ1, driving expansion of CD44v6 + epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial-mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues. MainIntestinal epithelial cells (IEC) 1 interact with innate lymphoid cells (ILC) 2 to form a dynamic barrier between organisms and their environment. Together, they are capable of rapidly responding to danger and damage in an antigen non-specific manner. For instance, type-3 ILC3 secrete Interleukin-22 (IL-22, Il22 ) in response to extracellular pathogens, which promotes anti-microbial peptide secretion and proliferation of Lgr5 + CD44 + intestinal stem cells 3 .Conversely, type-1 ILC express Interferon-gamma (IFNγ, Ifng ) in response to intracellular pathogens, and are comprised of circulating natural killer (NK) cells and tissue resident helper-like ILC1 (ILC1), which are considered less cytotoxic than their NK-cell counterparts 4 .Notably, ILC1 accumulate in the inflamed intestines of Inflammatory Bowel Disease (IBD) patients 5 , however the nature of their subset-specific interactions with the epithelium has remained elusive. Understanding the impact of ILC1 enrichment could offer novel avenues for treating this complex disease, which is a pressing issue as only a third of patients respond to gold standard TNFα-blocking biologics 6 .Teasing apart the role of rare cell populations in multifactorial diseases is challenging, and redundant cytokine signalling pathways in vivo can obscure ILC-specific phenotypes. Thus, to explore the impact of ILC1 on IEC we developed a reductionist co-culture system with murine small intestine organoids (SIO) 7 . We unexpectedly found that ILC1-derived TGFβ1 induces p38γ activity to drive epithelial Cd44v6 expression and SIO proliferation. Pathway analysis of co-culture transcriptomes also predicted ILC1-driven matrisome remodelling, so we developed highly defined PEG-based hydrogels to quantitatively characterize the impact of ILC1 on matrix remodelling in a human iPSC-derived organoid model (HIO) 8 . We not only confirmed that IBD patient-derived ILC1 express TGFB1 and upregulate CD44v6, but also that they p...

show abstract

Bi-directional cell-pericellular matrix interactions direct stem cell fate

Cited by 103 publications

References 73 publications

Adhesive Hydrogels for Maxillofacial Tissue Regeneration Using Minimally Invasive Procedures

Adhesive Hydrogels for Maxillofacial Tissue Regeneration Using Minimally Invasive Procedures

Injectable Cardiac Cell Microdroplets for Tissue Regeneration

ILC1-derived TGFβ1 drives intestinal remodelling

Contact Info

Product

Resources

About