Effect of Composition of Lung Biomimetic Niche on the Mesenchymal Stem Cell Differentiation toward Alveolar Type II Pneumocytes

Macromol Biosci. 2023 Jun;23(6):e2300035. doi: 10.1002/mabi.202300035. Epub 2023 Apr 14.

Abstract

Pulmonary niche dynamically orchestrates the signals, such as proliferation or differentiation of mesenchymal stem cells (MSCs), which allows inducing tissue repair. Lung niche includes extracellular matrix (ECM), comprising hyaluronic acid (HA) and collagen (COLL), and several types of MSCs. Impaired ECM, in lung pathologies, makes the promising therapies based on MSCs ineffective, as it results in a reduced attachment and homing of MSCs, precluding their differentiation and viability. To overcome this problem, in this study a pulmonary biomimetic niche based on HA and COLL hydrogel is developed, with the specific aim to elucidate the role of COLL and HA/COLL semi-interpenetrating polymer networks (SIPNs) in directing the differentiation of MSCs into Alveolar Type II (ATII) cells. The effect of low (L), medium (M), and high (H) molecular weight (MW) HA is investigated, both like structural component of the SIPNs hydrogel and like trophic factor in cell culture media solution. HA in the culture media significantly improves surfactant protein (SP)-C expression (≈2 ng mL-1 ), without showing difference in the MW tested, compared to control only (≈1 ng mL-1 ). Furthermore, LMWHA/COLL hydrogel promotes the SPC expression (approximately two times) compared to COLL, MMWHA/COLL, and HMWHA/COLL hydrogels.

Keywords: alveolar differentiation; collagen; hyaluronic acid; hydrogels; mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Epithelial Cells* / metabolism
  • Biomimetics
  • Cell Differentiation
  • Collagen / pharmacology
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology
  • Hydrogels / chemistry
  • Mesenchymal Stem Cells*

Substances

  • Collagen
  • Hyaluronic Acid
  • Hydrogels