PRODUCT RECOMMENDATION

LAMININ-521LAMININ-411 and/or LAMININ-421


Buy human recombinant laminin cell culture substrates from BioLamina                                              Go to the BioLamina shop

Do you want us to contact you? Please klick here


PROTOCOL

Efficient differentiation of MSC-derived insulin-producing cells


VEIW ON DEMAND

Expansion and maintenance of pancreatic islets on human recombinant laminin

Webinar on expansion and maintenance of pancreatic islets on human recombinant laminin


CUSTOMER TESTIMONIAL  

HOW TO CULTURE PANCREATIC CELLS ON LAMININ SUBSTRATES

Endocrine pancreatic B cells require endothelial signals for normal function

Endocrine pancreatic β cells do not form a basement membrane (BM). Instead, the β cells require endothelial signals for their differentiation and for normal function (Lammert, 2003; Yoshitomi & Zaret, 2004). During late embryonic development, β cells express high levels of VEGF-A that attract endothelial cells that, in turn, form the vasculature of the islets (Lammert, 2003; Nikolova, 2006). β cells in VEGF-A deficient mice have shown to have reduced insulin gene expression compared to fully vascularized control islets (Nikolova, 2006).

The vascular basement membrane formed next to the β cells contains alpha-4 and alpha-5 laminin isoforms (Sixt, 2001). Immunostaining of fetal human pancreas suggests that laminin-411 is expressed (Petajaniemi, 2002), however, adult human islets have been suggested to be surrounded by a double BM containing both laminin-511 and laminin-411 but where the BM facing the human endocrine islet only contain laminin-511/521 (Virtanen, 2008). A study by Kantengwa et al. demonstrates the presence of the laminin receptor integrin a3β1 on primary and transformed rat islet cells, and an important role of β1 integrins in islet cell attachment and spreading in vitro (Kantengwa, 1997).

 

Laminin proteins stimulate B cell proliferation and insulin production in vitro

By using pancreas-specific laminins in cell culture, the biological environment of the pancreas can be mimicked, making pancreatic islet cells thrive. In a study by Dr. Doug Melton et al. they investigated which endothelial signals that promote β cell proliferation and function. They show that laminin isoforms -411 and -511 stimulate β1 integrin signaling–dependent insulin production in vitro (Nikolova, 2006). The authors suggest that treating islets with these biologically relevant laminin isoforms prior to transplantation could help maintain insulin production until new capillaries are formed in transplanted islets (Nikolova, 2006).


Several studies have also revealed an essential role of cell-to-matrix interactions mediated by laminin-332 in the function of isolated pancreatic islet cells. Integrins a3β1 and a6β1 have been identified in rat pancreatic B cells (Bosco, 2000; Parnaud, 2006) and β cells cultured on a laminin-332-rich matrix spread out and secreted twice more insulin in response to glucose compared to cells cultured on plastic, poly-L-lysine (Parnaud, 2006). Furthermore, laminin-332 promote proliferation of rat β cellsB cells culture on laminin express insulin and protected the cells from apoptosis induced by pro-inflammatory cytokines (Hammar, 2004). In a follow-up publication by Armanet et al, the authors show that laminin-332 play a physiologically relevant role in human islets since laminin-332 is expressed and secreted by human islets and since conditions inducing islet stresses, such as isolation procedure and cytokine exposure, enhances laminin-332 production (Armanet, 2009).

Primary pancreatic islets cultured on laminin express insulin.
Courtesy of Dr. Anna Domogatsakya, Karolinska Institutet. 

 

Laminin-411 is a potent differentiation inducer of insulin-producing cells

In a publication by Qu et al. they show that laminin-411 act as a potent differentiation inducer of UC-MSC into insulin producing cells (Qu et al., 2014). In the article, they show that laminin-411 induces the expression of pancreatic precursor markers and markedly up-regulate insulin expression, both at mRNA and protein level. More importantly, administration of laminin 411-induced insulin producing cells rapidly and significantly down-regulated fasting blood glucose levels, significantly reduced the HbA1c concentration and markedly improved the symptoms and survival of type-1 diabetic rats (Qu et al., 2014).

 

Laminin cultured pancreatic islets expand and maintain function ex vivo

Watch this lecture by Dr. Anna Domogatskaya from Karolinska Institutet, Sweden where she presents her unpublished results showing the effects alpha-4 and alpha-5 laminin isoforms has on mouse pancreatic islets in culture. The main results can be summarized as:

  • The pancreatic islets spread out into flattened adherent clusters
  • All endocrine cells types (alpha, beta, delta, PP-cells) of the islet start to proliferate
  • All the endocrine cell types maintain marker specific expression
  • The cultured islets maintain functional ability for glucose-dependent insulin release 

LAMININ KEY ADVANTAGES

  • Laminin isoforms -332, -411, -511 and -521 stimulate β cell proliferation and insulin production in vitro

  • Laminin act as a potent differentiation inducer of hPSC into insulin producing cells

  • Laminin induces the expression of pancreatic precursor markers and markedly up-regulate insulin expression, both at mRNA and protein level.

  • Administration of laminin-induced insulin producing cells rapidly and significantly down-regulated fasting blood glucose levels, reduced the HbA1c concentration and improved the symptoms and survival of type-1 diabetic rats

  • Laminin isoforms support long-term maintenence of primary pancreatic islets

  • Defined and xeno-free culture method for reproduceble experments

  • x
  • Expansion of human PSC

  • Clonal cell culture applications

  • Eye cells

  • Cardiac cells

  • Neural cells

  • Skeletal muscle cells

  • Kidney cells

  • Hepatic cells

  • Cancer cells

  • Lung cells

  • Intestinal cells

  • Pancreatic cells

  • Hematopoietic stem and progenitor cells

  • Mesenchymal stem cells

  • Animal stem cells

  • Endothelial cells

  • Normal and cancerous mammary cells

  • Epithelial cells

Laminin-521

Laminin-521 human stem cell matrix makes pluripotent stem cell culture easy in a defined, xeno-free and biologically relevant cell culture system.

  • x
  • Neural cells

  • Hepatic cells

  • Lung cells

  • Intestinal cells

  • Normal and cancerous mammary cells

  • Expansion of human PSC

  • Clonal cell culture applications

  • Eye cells

  • Cardiac cells

  • Skeletal muscle cells

  • Kidney cells

  • Cancer cells

  • Pancreatic cells

  • Hematopoietic stem and progenitor cells

  • Mesenchymal stem cells

  • Animal stem cells

  • Endothelial cells

  • Epithelial cells

Laminin-111

Laminin-111 is important during early epithelial development and differentiation of the epiblast, and is commonly used as a general attachment protein in cell culture.

  • x
  • Neural cells

  • Eye cells

  • Endothelial cells

  • Animal stem cells

  • Pancreatic cells

  • Epithelial cells

  • Cardiac cells

  • Cancer cells

  • Hepatic cells

  • Intestinal cells

  • Kidney cells

  • Lung cells

  • Skeletal muscle cells

  • Expansion of human PSC

  • Clonal cell culture applications

  • Hematopoietic stem and progenitor cells

  • Mesenchymal stem cells

  • Normal and cancerous mammary cells

LAMscreen

LAMscreen is a kit with all our currently available laminin isoforms so that you can easily screen the best laminins for different cell types.