Cord Blood Plasma and Placental Mesenchymal Stem Cells-Derived Exosomes Increase Ex Vivo Expansion of Human Cord Blood Hematopoietic Stem Cells While Maintaining Their Stemness

Rasha S Teleb; Amal Abdul-Hafez; Amira Othman; Ahmed El-Abd Ahmed; Abdelrahman A Elsaid; Hattan Arif; Ahmed A Zarea; Mohammed Abdulmageed; Hend Mohamed; Sherif Abdelfattah Ibrahim; Ranga P Thiruvenkataramani; Tarek Mohamed; Masamitsu Kanada; Burra V Madhukar; Myrna Gonzalez Arellano; Mohammed M Sayed; Heba M Qubaisy; Said A Omar

doi:10.3390/cells12020250

Cord Blood Plasma and Placental Mesenchymal Stem Cells-Derived Exosomes Increase Ex Vivo Expansion of Human Cord Blood Hematopoietic Stem Cells While Maintaining Their Stemness

Cells. 2023 Jan 7;12(2):250. doi: 10.3390/cells12020250.

Authors

Rasha S Teleb^{1

2}, Amal Abdul-Hafez¹, Amira Othman^{1

3}, Ahmed El-Abd Ahmed², Abdelrahman A Elsaid⁴, Hattan Arif¹, Ahmed A Zarea^{5

6}, Mohammed Abdulmageed^{1

3}, Hend Mohamed¹, Sherif Abdelfattah Ibrahim^{1

7}, Ranga P Thiruvenkataramani^{1

3}, Tarek Mohamed^{1

3}, Masamitsu Kanada^{5

8}, Burra V Madhukar¹, Myrna Gonzalez Arellano^{1

3}, Mohammed M Sayed², Heba M Qubaisy², Said A Omar^{1

3}

Affiliations

¹ Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA.
² Department of Pediatrics and Neonatology, Faculty of Medicine, South Valley University, Qena 83523, Egypt.
³ Regional Neonatal Intensive Care Unit, Sparrow Hospital, Lansing, MI 48912, USA.
⁴ Clinical Pathology Department, Faculty of Medicine, South Valley University, Qena 83523, Egypt.
⁵ The Institute for Quantitative Health Science & Engineering, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA.
⁶ Cell and Molecular Biology Program, Michigan State University, East Lansing, MI 48824, USA.
⁷ Histology and Cell Biology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
⁸ Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA.

Abstract

Background: Mesenchymal stem cells (MSCs) have been used for ex vivo expansion of umbilical cord blood (UCB) hematopoietic stem cells (HSCs) to maintain their primitive characters and long-term reconstitution abilities during transplantation. Therapeutic effects of MSCs mainly rely on paracrine mechanisms, including secretion of exosomes (Exos). The objective of this study was to examine the effect of cord blood plasma (CBP)-derived Exos (CBP Exos) and Placental MSCs-derived Exos (MSCs Exos) on the expansion of UCB HSCs to increase their numbers and keep their primitive characteristics.

Methods: CD34⁺ cells were isolated from UCB, cultured for 10 days, and the expanded HSCs were sub-cultured in semisolid methylcellulose media for primitive colony forming units (CFUs) assay. MSCs were cultured from placental chorionic plates.

Results: CBP Exos and MSCs Exos compared with the control group significantly increased the number of total nucleated cells (TNCs), invitro expansion of CD34⁺ cells, primitive subpopulations of CD34⁺38⁺ and CD34⁺38^-Lin^- cells (p < 0.001). The expanded cells showed a significantly higher number of total CFUs in the Exos groups (p < 0.01).

Conclusion: CBP- and placental-derived exosomes are associated with significant ex vivo expansion of UCB HSCs, while maintaining their primitive characters and may eliminate the need for transplantation of an additional unit of UCB.

Keywords: exosomes; extracellular vesicles (EVs); hematopoietic stem cells; mesenchymal stem cells; placenta; umbilical cord; umbilical cord blood transplantation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Proliferation
Exosomes*
Female
Fetal Blood
Hematopoietic Stem Cells
Humans
Mesenchymal Stem Cells*
Placenta
Pregnancy

Grants and funding

S.A.O., T.M. and R.P.T. received funding for this research from the Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State university, East Lansing Michigan. M.A. and M.G.A. received funding for this research from the graduate medical education (GME) at Sparrow hospital, Lansing, Michigan and the neonatology fellowship at Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing Michigan. R.S.T. received funding for this research from the government of Arab Republic of Egypt via the Egyptian cultural & Educational Bureau, Embassy of Egypt in Washington, DC.