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

• Published in: Macromolecular bioscience 2023-06, Vol.23 (6), p.e2300035-n/a
• Main Authors: Della Sala, Francesca, di Gennaro, Mario, Lista, Gianluca, Messina, Francesco, Valente, Teodoro, Borzacchiello, Assunta
• Format: Article
• Language: English
• Subjects: alveolar differentiation; Alveolar Epithelial Cells - metabolism; Alveoli; Biomimetics; Cell culture; Cell Differentiation; Cell proliferation; collagen; Collagen - pharmacology; Composition effects; Culture media; Differentiation (biology); Extracellular matrix; Hyaluronic acid; Hyaluronic Acid - chemistry; Hyaluronic Acid - pharmacology; Hydrogels; Hydrogels - chemistry; Interpenetrating networks; Lungs; Mesenchymal Stem Cells; Molecular weight; Pneumocytes; Polymers; Stem cells
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.202300035

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. In this study, a pulmonary biomimetic niche based on hyaluronic acid (HA) and collagen (COLL) hydrogel semi‐interpenetrating polymer networks is developed, aiming to elucidate the role of these constituents in directing the differentiation of mesenchymal stem cells into Alveolar Type II cells. Low MWHA/COLL hydrogel promotes the surfactant protein‐C expression compared to COLL, medium MWHA/COLL, and high M WHA/COLL hydrogels.