Timoneri F, Lo Iacono M, Corrao S, Alberti G, Amico G, Corsello T, Conaldi P G, Russo Eleonora, La Rocca G
Department of Regenerative Medicine and Immunotherapy - Ri.MED Foundation, Palermo, Italy.
Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, Palermo, Italy.
Front Cell Dev Biol. 2025 Jun 24;13:1626353. doi: 10.3389/fcell.2025.1626353. eCollection 2025.
The umbilical cord (UC) is a perinatal tissue from which it is possible to isolate mesenchymal stromal cells (MSCs) with a higher proliferation rate and a higher differentiation capacity compared to their adult counterparts. Wharton's jelly (WJ) is a rich source of multipotent and hypoimmunogenic MSCs (WJ-MSCs), which are considered promising candidates for cell therapy of many conditions, including liver diseases. Preterm umbilical cord (birth before 37 weeks of gestation) is generally considered a waste product, so its use does not affect ethical issues. Similarly to the full-term UC, it can be considered a valid source of WJ-MSCs, although little is known about their phenotype and differentiation capacity. We aim to show that WJ-MSCs derived from preterm umbilical cords exhibit comparable characteristics to their mature counterparts and, in particular, show a similar ability to differentiate into hepatocyte-like cells and retain hypoimmunogenicity features. Both these aspects may be key in the prospective application of these cells in regenerative medicine.
Here, we isolated WJ-MSCs from seven prematurely harvested umbilical cords (pWJ-MSCs). We assessed a mesenchymal phenotype and differentiation potential by flow cytometry, immunocytochemistry, and immunofluorescence. A standardized liver differentiation protocol was performed, and the acquisition of the hepatic phenotype was assessed by characterization of hepatic protein expression and functional assays.
We demonstrated that pWJ-MSCs exhibited mesenchymal characteristics, acquired phenotypical and functional features of hepatocytes when induced to differentiate in a specific medium, and maintained the expression of immunomodulatory molecules.
This study showed that even if pregnancy has been interrupted before the 22nd week, p-WJ-MSCs had the same differentiative ability as the counterpart derived from the full-term UC, that we have previously demonstrated, and can be considered a valid cellular population for liver cell therapy.
脐带是一种围产期组织，与成年后的间充质基质细胞相比，从中分离出的间充质基质细胞具有更高的增殖率和分化能力。华通胶是多能且低免疫原性的间充质基质细胞（华通胶间充质基质细胞）的丰富来源，这些细胞被认为是包括肝脏疾病在内的多种病症细胞治疗的有前景候选者。早产脐带（妊娠37周前出生）通常被视为废品，因此其使用不涉及伦理问题。与足月脐带类似，它可被视为华通胶间充质基质细胞的有效来源，尽管对其表型和分化能力了解甚少。我们旨在表明，源自早产脐带的华通胶间充质基质细胞具有与其成熟对应物相当的特征，特别是表现出类似的分化为肝细胞样细胞的能力，并保留低免疫原性特征。这两个方面对于这些细胞在再生医学中的前瞻性应用可能至关重要。
在此，我们从七根早产收获的脐带中分离出华通胶间充质基质细胞（早产华通胶间充质基质细胞）。我们通过流式细胞术、免疫细胞化学和免疫荧光评估间充质表型和分化潜能。执行标准化的肝脏分化方案，并通过肝脏蛋白表达表征和功能测定评估肝细胞表型的获得情况。
我们证明早产华通胶间充质基质细胞表现出间充质特征，在特定培养基中诱导分化时获得肝细胞的表型和功能特征，并维持免疫调节分子的表达。
本研究表明，即使妊娠在第22周前中断，早产华通胶间充质基质细胞也具有与我们之前证明的源自足月脐带的对应物相同的分化能力，并且可被视为肝细胞治疗的有效细胞群体。
