Biologically Relevant Laminins in Regenerative Medicine

  • Anna Domogatskaya
  • Sergey Rodin
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)


Need for biologically relevant coatings in regenerative medicine. Recent advances in stem cell-based regenerative medicine allow to expand human cells in almost unlimited amounts. However, expanded cells become devoid of natural niche cues and, therefore, may become prone to risks of function loss and malignant transformation. In order to maintain the expanded cells in a safe and functional way, one has to imitate in vitro the natural niche, comprising biologically relevant extracellular matrix molecules. For majority of cell types, including neurons, insulin-producing β-cells and vascular endothelial cells, biologically relevant laminins are essential part of natural niche. Laminins: 16 tissue-specific isoforms that mediate cell maintenance and behavior. Laminins (LM) are large, cross-shaped molecules that convey extracellular matrix cues via cell receptors to cell signaling systems and thus affect cell maintenance and behavior. Laminins can mediate behavior of associated cells, such as survival, adhesion, migration, proliferation, phenotype maintenance or differentiation. Each of known 16 laminin isoforms has unique biological function; mutations in laminin-encoding genes often result in severe pathologies or lethality. Despite molecular structure similarity and evolutionary homology, certain laminin isoforms may exert antagonistic effects on cell behavioral patterns. Importantly, biologically relevant laminins act in synergy with specific growth factors and cell–cell contact molecules, such as E-cadherin. Lack of either may result in malfunctioning cell culture systems. Lack of biologically relevant laminins may result in cell apoptosis, phenotype loss, or malignant transformation. Survival pathways for majority of mammalian cells depend on niche-specific extracellular matrix anchorage. Lack of such anchorage or irrelevant anchorage triggers apoptotic pathways and results in anoikis (apoptosis, caused by lack of relevant anchorage). In the absence of biologically relevant matrix cues, cells may undergo apoptosis or activate malignant pathways of anchorage-independent anti-apoptotic signaling. Majority of mammalian cell types depend on interaction with biologically relevant laminins. Biologically relevant laminins benefit quality cell culture in vitro. In vitro, cell culture systems based on use of niche-specific laminins are described for human and mouse embryonic stem cells, hematopoietic stem cells, neurons and Schwann cells, insulin-producing β-cells, and other cell types. We shall discuss success criteria and possible pitfalls for generating laminin-based safe, robust, and efficient technologies for culturing other cell types needed to treat various diseases.


Laminin Embryonic stem cell Stem cell Extracellular matrix Regenerative medicine Neuron Pancreatic islets Insulin-producing beta cell Stem cell technologies Proliferation Survival Apoptosis Differentiation Adhesion Safety Cell culture Signaling Integrin 



This work was supported by Swedish Research Council (project 2016-01831, A.D.), Foundation for Assistance to Small Innovative Enterprises (project 24026, A.D.) and Russian Science Foundation (project 14-15-00712, A.D.).


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Transplantation Surgery, Department of Clinical Science, Intervention and TechnologyKarolinska InstituteHuddingeSweden
  2. 2.Department of Medical Biochemistry and BiophysicsKarolinska InstituteStockholmSweden

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