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Morbid Cell Status and Donor Age Significantly Alter Mesenchymal Stem Cell Functionality and Reparability

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Handbook of Stem Cell Applications

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Abstract

Bone marrow (BM)-derived mesenchymal stem cells (MSCs) differentiate into specialized tissues, including cardiomyocytes, endothelial cells, and smooth muscle cells. Indeed, their demonstrated multi-lineage differentiation potential, lower immunoreactivity, paracrine activity, and availability from the autologous source make these cells superior candidates for myocardial repair and regeneration. Currently, BM-derived MSCs are being used in Phase-III pivotal trials in larger groups of patients to assess their myocardial reparability. However, these studies have reported less-than-optimal outcomes than preclinical and translational results. While reasoning out the modest clinical outcome, we hypothesized that autologous cells from elderly donors with comorbidities may be less efficacious than allogeneic cells from young, healthy donors due to chronological aging and disease-induced cellular stress and morbidity. This chapter primarily aims to provide an overview of the published data to highlight the factors responsible for the modest outcome observed in clinical settings, especially concerning the donors’ age and morbid health status.

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Abbreviations

ALL:

Acute lymphoblastic leukemia

AML:

Acute myelogenous leukemia

BM:

Bone marrow

BME:

Bone marrow edema

BMP:

Bone morphogenic protein

BT:

Beta thalassemia

CML:

Chronic myelocytic leukemia

CYT:

Cytarabine

DAU:

Daunorubicin

DM:

Diabetes mellitus

ECM:

Extracellular matrix

FAK:

Focal adhesion protein kinase

FGF:

Fibroblast growth factor

HIF:

Hypoxia-inducible growth factor

HO:

Heme oxygenase

HSCs:

Hematopoietic stem cell

IGF:

Insulin-like growth factor

IHD:

Ischemic heart disease

LVEF:

Left ventricular ejection fraction

MDS:

Myelodysplastic syndrome

MI:

Myocardial infarction

MSCs:

Mesenchymal stem cells

NPY:

Neuropeptide-Y

NPY5R:

Neuropeptide-Y5 receptor

OA:

Osteoarthritis

SASP:

Senescence-associated secretory phenotype

SCD:

Sickle cell disease

SDF:

Stromal Cell-Derived Factor

SKMs:

Skeletal myoblasts

SMCs:

Smooth muscle cells

TLR:

Toll-like receptor

UPR:

Unfolded protein response

VEGF:

Vascular endothelial growth factor

Vin:

Vincristine

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  1. Department of Basic Sciences, Sulaiman AlRajhi University, Al Bukayriyah, Kingdom of Saudi Arabia

    Moaz Safwan, Mariam Safwan Bourgleh, Hani Alshakaki, Abdullah Molhem & Khawaja Husnain Haider

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Correspondence to Khawaja Husnain Haider .

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    Khawaja H. Haider

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Safwan, M., Bourgleh, M.S., Alshakaki, H., Molhem, A., Haider, K.H. (2023). Morbid Cell Status and Donor Age Significantly Alter Mesenchymal Stem Cell Functionality and Reparability. In: Haider, K.H. (eds) Handbook of Stem Cell Applications. Springer, Singapore. https://doi.org/10.1007/978-981-99-0846-2_62-1

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