Laminin a4 Deficient Mice Exhibit Decreased Capacity for Adipose Tissue Expansion and Weight Gain

Vaicik M.K., Thyboll Kortesmaa J., Movérare-Skrtic S., Kortesmaa J., Soininen R., Bergström G., Ohlsson C., Chong L.Y., Rozell B., Emont M., Cohen R.N., Brey E.M., Tryggvason K.
PLOS ONE, 2014

Staining was performed for known adipose tissue BM proteins. In wild-type control mice the a2 and a4 chains of laminin were present in the BM surrounding mature adipocytes. Laminin a5 was not observed in mouse adipocyte BM. In this manuscript we describe the role of laminin a4, a specialized ECM protein surrounding adipocytes, on weight gain and adipose tissue function. Adipose tissue accumulation, lipogenesis, and structure were examined in mice with a null mutation of the laminin a4 gene (Lama42/2) and compared to wild-type (Lama4+/+) control animals. Lama42/2 mice exhibited reduced weight gain in response to both age and high fat diet. Interestingly, the mice had decreased adipose tissue mass and altered lipogenesis in a depot-specific manner. In particular, epididymal adipose tissue mass was specifically decreased in knock-out mice, and there was also a defect in lipogenesis in this depot as well. In contrast, no such differences were observed in subcutaneous adipose tissue at 14 weeks. The results suggest that laminin a4 influences adipose tissue structure and function in a depot-specific manner.


Differentiation-dependent Expression of Laminin-8 (α4β1γ1) mRNAs in Mouse 3T3-L1 Adipocytes

Niimi T., Kumagai C., Okano M., Kitagaw Y.
Matrix Biology, 1997

Here, the uthors report that laminin-411 is the specific isoform of laminin synthesized in adipocytes. Reverse transcription-polymerase chain reaction (RT-PCR) of mRNA from mouse 3T3-L1 cells yielded amplified fragments only for α4β1γ1. Northern blots showed that the levels of α4,β1 and γ1 mRNAs increased 2.5-fold during adipose conversion of 3T3-L1 cells. A 1062 bp cDNA fragment cloned by RT-PCR demonstrated a polymorphism in the mouse a4 gene which would lead to five amino acid changes in the domain G.


The role of adipose protein derived hydrogels in adipogenesis

Uriel S. Huang J-J., Moya M.L., Francis M.E., Wang R., Chang S-Y., Cheng M-H., Brey E.M.
Biomaterials, 2008

The present study, the authors investigates the potential of adipose derived matrices to induce adipogenesis in vitro and in vivo. Solutions containing basement membrane proteins and growth factors were extracted from subcutaneous adipose tissue. The extracts contain a complex mix of proteins, including laminin a4, collagen IV, nidogen and fibronectin. These extracts could be induced to form gels by either incubating the solutions at 37 degrees C or adjusting the pH to 4.0. The adipose extracts promoted rapid pre-adipocyte aggregation and formation of lipid-loaded colonies in vitro. Differentiation on adipose-derived gels was greater than tissue culture dishes and Matrigel. Significant adipose formation was observed when adipose-derived gels were implanted around a rat epigastric pedicle bundle. Adipose levels in these gels were significantly greater than Matrigel. These adipose-derived hydrogels promote rapid adipogenesis in vitro and in vivo and may lead to new materials for adipose tissue engineering, and provide an environment for studying cell–matrix interactions in adipogenesis.


Human Mesenchymal Cells from Adipose Tissue Deposit Laminin and Promote Regeneration of Injured Spinal Cord in Rats

Menezes K., Nascimento M.A., Goncalves J.P., Silva Cruz A., Vieira Lopes D., Curzio B., Bonamino M., Ricardo J., de Menezes L., Borojevic R., Doria Rossi M.I., Coelho-Sampaio T.
PLOS ONE, 2013

Bone marrow stromal cells have been shown to express laminin α4, α5, β1, β2 and γ1. Here we tested whether hADSCs in vitro produced these laminin chains, but we found reactivity only for β2 and γ1. In addition, we found no positivity for the α2 chain, which, together with α5, β2 and γ1, was detected in vivo. Considering that laminin α2 and α5 of human origin appeared in spinal cord of rats injected with hADSCs (injured or uninjured), we propose that the exposure of the cells to the spinal cord environment was capable of switching the production of laminin chains α2 and α5. These laminin chains secreted only after transplantation of hADSC may stimulate the proliferation and migration of neural precursors from the ependymal layer around the central canal or from other neurogenic niches around blood vessels. The attracted precursor cells accumulate mainly in the lesion site, contributing to regeneration of the nervous tissue and ultimately to functional recovery. Adipose deriverade MSC start producing a5 och a2 laminin in vivo and the authors show that it’s the secretion of laminin that have the therapeutic effect (important aspect for herapy). In line with this hypothesis, it has previously been shown that laminin isoforms containing the α chains 2, 4 and 5 are essential components of the subependymal neurogenic niche of adult mice.


Modifying alginate with early embryonic extracellular matrix, laminin, and hyaluronic acid for adipose tissue engineering

Chen Y-S., Chen Y-Y., Hsueh Y-S., Tai H-C., Lin F-H.
J Biomed Mater Res Part A, 2015

In this study, a new material, HA-L-Alg, was synthesized by linking developmentally essential ECM constituents hyaluronic acid (HA) and laminin (Life technologies) to alginate (Alg). The fabrication of HA-LAlg was confirmed by FTIR spectroscopy, and it was used to form 3D cell-carrying beads. HA-L-Alg beads had a steady rate of degradation and retained 63.25% of mass after 9 weeks. HA-L-Alg beads showed biocompatibility comparable to beads formed by Alg-only with no obvious cytotoxic effect on the embedded 3T3-L1 preadipocytes. HA-L-Alg encapsulated 3T3-L1 cells were found to have a higher proliferation rate over those in Alg-only beads. These cells also showed better differentiation capacity after 2 weeks of adipogenic induction within HA-L-Alg beads. These results support that HA-L-Alg facilitated cell survival and proliferation, as well as stimulated and maintained cell differentiation.