Mesenchymal Stromal Cells

Integrin-Mediated Regulation of MSC Identity and Function

In tissues, laminin forms a critical link between the extracellular matrix (ECM) and cells, regulating cellular identity, proliferation, and survival in both pluripotent and adult stem cell niches. Full-length laminins, unlike fragmented laminin products, activate core signaling pathways by engaging all relevant cell surface receptors, including integrins (α6β1), dystroglycans, and syndecans. Moreover, only full-length laminins are capable of self-polymerizing and forming ECM-like networks, allowing interaction with other ECM components.

The functions of mesenchymal stromal cells (MSCs) are tightly regulated by interactions with their microenvironment, where survival and differentiation potential are controlled by intrinsic mechanosignaling pathways. Integrin α6, also known as CD49f (ITGA6), plays a key role in MSC self-renewal and the maintenance of stemness through direct transcriptional regulation of pluripotency factors OCT4 and SOX2 (Yu et al., 2012). Integrin α6 is highly expressed in early progenitor cells, supporting higher proliferation rates and greater differentiation potential; however, its expression declines with passaging (Yang et al., 2015). Additionally, crosstalk between CD146, a receptor for laminin α4, and CD49f expression is required for the adipogenic and osteogenic differentiation of MSCs (Tran et al., 2023).

References:

Yu et al., 2012 Stem Cells. CD49f Enhances Multipotency and Maintains Stemness Through the Direct Regulation of OCT4 and SOX2†

Yang et al., 2015 Cells. CD49f Acts as an Inflammation Sensor to Regulate Differentiation, Adhesion, and Migration of Human Mesenchymal Stem Cells

Tran et al., 2023 Cells. CD49f and CD146: A Possible Crosstalk Modulates Adipogenic Differentiation Potential of Mesenchymal Stem Cells.

Use of LN521 in Engineering Tissue-Like MSC Structures

Coating non-conventional surfaces with LN521 has enabled new tissue engineering strategies. Jiang et al. (2017) developed a protocol for generating light-induced cell sheets on TiO₂ nanodots, an innovative method to recreate 3D tissue-like structures from bone marrow-derived mesenchymal stem cells (BMSCs). LN521 enhanced the adhesion of rat BMSCs to nanodot films in a concentration-dependent manner, outperforming other substrates and enabling the formation of intact BMSC layers. Coating with LN521 also promoted efficient cell proliferation, maintained high cell viability, and preserved differentiation potential into osteogenic, adipogenic, and chondrogenic lineages (Figure 1).

References

Jiang et al., 2017 Biomed Research International Laminin-521 Promotes Rat Bone Marrow Mesenchymal Stem Cell Sheet Formation on Light-Induced Cell Sheet Technology

Selecting the Right Substrate for Efficient MSC Differentiation

Culture conditions, particularly cell-matrix interactions, strongly influence the biomechanical properties of MSCs and play a crucial role in directing cell fate. Selecting a biologically relevant substrate is key to achieving efficient and precise differentiation. Recent studies demonstrate that LN521 serves as an optimal substrate for promoting mineralization of induced MSC (iMSC)-derived osteoblasts, supporting differentiation under both normoxic and hypoxic conditions by ensuring proper cell attachment and providing a native-like microenvironment (Tian et al., 2022; Danalache et al., 2025).

References:
Tian et al., 2022 Journal of Materials Chemistry B. Effect of extracellular matrix proteins on the differentiation of human pluripotent stem cells into mesenchymal stem cells.

Danalache et al., 2024 Bioengineering. Mesenchymal Stem Cell Plasticity: What Role Do Culture Conditions and Substrates Play in Shaping Biomechanical Signatures?