Wharton's Jelly Mesenchymal Stromal Cells As a Feeder Layer for the Ex Vivo Expansion of Hematopoietic Stem and Progenitor Cells: a Review

Overview

Journal Stem Cell Rev Rep

Publisher Springer

Specialty Cell Biology

Date 2016 Nov 18

PMID 27853939

Citations 14

Authors

Melania Lo Iacono

Rita Anzalone

Giampiero La Rocca

Elena Baiamonte

Aurelio Maggio

Santina Acuto

Affiliations

Soon will be listed here.

Abstract

In recent years, umbilical cord blood (UCB) has been widely used as an alternative source to bone marrow (BM) for transplantation of hematopoietic stem and progenitor cells (HSPCs) in a variety of hematological and non-hematological disorders. Nevertheless, the insufficient number of UCB-HSPCs for graft represents a major challenge. HSPCs ex vivo expansion prior to transplantation is a valid strategy to overcome this limit. Several attempts to optimize the expansion conditions have been reported, including the use of mesenchymal stromal cells (MSCs) as feeder layer. Wharton's Jelly (WJ), the main component of umbilical cord (UC) matrix, is especially rich in MSCs, which are considered ideal candidates for feeder layer in co-culture systems. In fact, they can be easily harvested and grow robustly in culture, producing a confluent monolayer in a short time. Similarly to bone marrow-mesenchymal stromal cells (BM-MSCs), WJ-derived MSCs (WJ-MSCs) have been used to support hematopoiesis in vitro and in vivo. Here, we review the rationale for using MSCs, particularly WJ-MSCs, as a feeder layer for UCB-HSPCs ex vivo expansion. In addition, we report the main findings attesting the use of these MSCs as a support in hematopoiesis.

Citing Articles

Characterization and Proteomic Profiling of Hepatocyte-like Cells Derived from Human Wharton's Jelly Mesenchymal Stromal Cells: De Novo Expression of Liver-Specific Enzymes.

Lo Iacono M, Corrao S, Alberti G, Amico G, Timoneri F, Russo E Biology (Basel). 2025; 14(2).

PMID: 40001892 PMC: 11851833. DOI: 10.3390/biology14020124.

Wharton's jelly stem cells delivered via a curcumin-loaded nanofibrous wound dressings improved diabetic wound healing via upregulating VEGF and IGF genes: An in vitro and in vivo study.

Chen C, Zhao H, Zhang W, Hong X, Li S, Rohani S Regen Ther. 2024; 26:547-556.

PMID: 39210999 PMC: 11359744. DOI: 10.1016/j.reth.2024.06.018.

The Truth Is Out There: Biological Features and Clinical Indications of Extracellular Vesicles from Human Perinatal Stem Cells.

Russo E, Alberti G, Corrao S, Borlongan C, Miceli V, Conaldi P Cells. 2023; 12(19).

PMID: 37830562 PMC: 10571796. DOI: 10.3390/cells12192347.

Recent advances in engineering hydrogels for niche biomimicking and hematopoietic stem cell culturing.

Huang X, Wang Y, Wang T, Wen F, Liu S, Oudeng G Front Bioeng Biotechnol. 2022; 10:1049965.

PMID: 36507253 PMC: 9730123. DOI: 10.3389/fbioe.2022.1049965.

Wharton's jelly-derived stromal cells and their cell therapy applications in allogeneic haematopoietic stem cell transplantation.

Pochon C, Notarantonio A, Laroye C, Reppel L, Bensoussan D, Bertrand A J Cell Mol Med. 2022; 26(5):1339-1350.

PMID: 35088933 PMC: 8899189. DOI: 10.1111/jcmm.17105.

References

Wilson A, Trumpp A . Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol. 2006; 6(2):93-106. DOI: 10.1038/nri1779. View

Fong C, Gauthaman K, Cheyyatraivendran S, Lin H, Biswas A, Bongso A . Human umbilical cord Wharton's jelly stem cells and its conditioned medium support hematopoietic stem cell expansion ex vivo. J Cell Biochem. 2011; 113(2):658-68. DOI: 10.1002/jcb.23395. View

Bari S, Seah K, Poon Z, Sze Cheung A, Fan X, Ong S . Expansion and homing of umbilical cord blood hematopoietic stem and progenitor cells for clinical transplantation. Biol Blood Marrow Transplant. 2015; 21(6):1008-19. DOI: 10.1016/j.bbmt.2014.12.022. View

Magin A, Korfer N, Partenheimer H, Lange C, Zander A, Noll T . Primary cells as feeder cells for coculture expansion of human hematopoietic stem cells from umbilical cord blood--a comparative study. Stem Cells Dev. 2008; 18(1):173-86. DOI: 10.1089/scd.2007.0273. View

Leisten I, Kramann R, Ventura Ferreira M, Bovi M, Neuss S, Ziegler P . 3D co-culture of hematopoietic stem and progenitor cells and mesenchymal stem cells in collagen scaffolds as a model of the hematopoietic niche. Biomaterials. 2011; 33(6):1736-47. DOI: 10.1016/j.biomaterials.2011.11.034. View

Brown J, Boussiotis V . Umbilical cord blood transplantation: basic biology and clinical challenges to immune reconstitution. Clin Immunol. 2008; 127(3):286-97. PMC: 2468219. DOI: 10.1016/j.clim.2008.02.008. View

Batsali A, Kastrinaki M, Papadaki H, Pontikoglou C . Mesenchymal stem cells derived from Wharton's Jelly of the umbilical cord: biological properties and emerging clinical applications. Curr Stem Cell Res Ther. 2013; 8(2):144-55. DOI: 10.2174/1574888x11308020005. View

Anzalone R, Lo Iacono M, Loria T, Di Stefano A, Giannuzzi P, Farina F . Wharton's jelly mesenchymal stem cells as candidates for beta cells regeneration: extending the differentiative and immunomodulatory benefits of adult mesenchymal stem cells for the treatment of type 1 diabetes. Stem Cell Rev Rep. 2010; 7(2):342-63. DOI: 10.1007/s12015-010-9196-4. View

Chan C, Wu K, Lee Y, Hwang S, Lee M, Liao S . The comparison of interleukin 6-associated immunosuppressive effects of human ESCs, fetal-type MSCs, and adult-type MSCs. Transplantation. 2012; 94(2):132-8. DOI: 10.1097/TP.0b013e31825940a4. View

10.

Kadereit S, Deeds L, Haynesworth S, Koc O, Kozik M, Szekely E . Expansion of LTC-ICs and maintenance of p21 and BCL-2 expression in cord blood CD34(+)/CD38(-) early progenitors cultured over human MSCs as a feeder layer. Stem Cells. 2002; 20(6):573-82. DOI: 10.1634/stemcells.20-6-573. View

11.

Peled T, Shoham H, Aschengrau D, Yackoubov D, Frei G, Rosenheimer G N . Nicotinamide, a SIRT1 inhibitor, inhibits differentiation and facilitates expansion of hematopoietic progenitor cells with enhanced bone marrow homing and engraftment. Exp Hematol. 2011; 40(4):342-55.e1. DOI: 10.1016/j.exphem.2011.12.005. View

12.

Ventura Ferreira M, Labude N, Walenda G, Adamzyk C, Wagner W, Piroth D . Ex vivo expansion of cord blood-CD34(+) cells using IGFBP2 and Angptl-5 impairs short-term lymphoid repopulation in vivo. J Tissue Eng Regen Med. 2012; 7(12):944-54. DOI: 10.1002/term.1486. View

13.

Mayani H . Notch signaling: from stem cell expansion to improving cord blood transplantation. Expert Rev Hematol. 2010; 3(4):401-4. DOI: 10.1586/ehm.10.37. View

14.

Bennaceur-Griscelli A, Pondarre C, Schiavon V, Vainchenker W, Coulombel L . Stromal cells retard the differentiation of CD34(+)CD38(low/neg) human primitive progenitors exposed to cytokines independent of their mitotic history. Blood. 2001; 97(2):435-41. DOI: 10.1182/blood.v97.2.435. View

15.

Sarugaser R, Lickorish D, Baksh D, Hosseini M, Davies J . Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells. 2005; 23(2):220-9. DOI: 10.1634/stemcells.2004-0166. View

16.

Lewis I, Verfaillie C . Multi-lineage expansion potential of primitive hematopoietic progenitors: superiority of umbilical cord blood compared to mobilized peripheral blood. Exp Hematol. 2000; 28(9):1087-95. DOI: 10.1016/s0301-472x(00)00515-4. View

17.

Nauta A, Fibbe W . Immunomodulatory properties of mesenchymal stromal cells. Blood. 2007; 110(10):3499-506. DOI: 10.1182/blood-2007-02-069716. View

18.

de Wynter E, Emmerson A, Testa N . Properties of peripheral blood and cord blood stem cells. Baillieres Best Pract Res Clin Haematol. 2000; 12(1-2):1-17. DOI: 10.1053/beha.1999.0003. View

19.

Valencic E, Piscianz E, Andolina M, Ventura A, Tommasini A . The immunosuppressive effect of Wharton's jelly stromal cells depends on the timing of their licensing and on lymphocyte activation. Cytotherapy. 2010; 12(2):154-60. DOI: 10.3109/14653240903493417. View

20.

Lewis I, Almeida-Porada G, Du J, Lemischka I, Moore K, Zanjani E . Umbilical cord blood cells capable of engrafting in primary, secondary, and tertiary xenogeneic hosts are preserved after ex vivo culture in a noncontact system. Blood. 2001; 97(11):3441-9. DOI: 10.1182/blood.v97.11.3441. View