Extension of Maximal Lifespan and High Bone Marrow Chimerism After Nonmyeloablative Syngeneic Transplantation of Bone Marrow From Young to Old Mice.

Marina V Kovina,Elena V Bogdanenko,Maxim V Balyasin,Tatyana G Dyuzheva,Larisa A Sergievich,Yury M Khodarovich,Artem L Kovin,Elena V Karnaukhova,Alexey V Karnaukhov,Mikhail E Krasheninnikov,Alexey V Lyundup,Sarul T Gazheev

doi:10.3389/fgene.2019.00310

Marina V Kovina, Elena V Bogdanenko + Show 10 more

Open Access

https://doi.org/10.3389/fgene.2019.00310

Copy DOI

Abstract

The goal of this work was to determine the effect of nonablative syngeneic transplantation of young bone marrow (BM) to laboratory animals (mice) of advanced age upon maximum duration of their lifespan. To do this, transplantation of 100 million nucleated cells from BM of young syngeneic donors to an old nonablated animal was performed at the time when half of the population had already died. As a result, the maximum lifespan (MLS) increased by 28 ± 5%, and the survival time from the beginning of the experiment increased 2.8 ± 0.3-fold. The chimerism of the BM 6 months after the transplantation was 28%.

Highlights

Increasein maximum lifespan (MLS) is the most significant indicator of hitting the basic mechanisms of aging, in particular, regarding age-related loss of stem cells (Colvin et al, 2004) and cell damage accumulation (Kujoth et al, 2005; Baar et al, 2017)
Two groups of recipient mice were used for the experiments
All the recipients were green fluorescent protein (GFP)-negative mice of B10-GFP line, which is heterozygous for the GFP transgene

Summary

Introduction

Increasein maximum lifespan (MLS) is the most significant indicator of hitting the basic mechanisms of aging, in particular, regarding age-related loss of stem cells (Colvin et al, 2004) and cell damage accumulation (Kujoth et al, 2005; Baar et al, 2017). Our in vitro studies showed that under certain conditions undifferentiated stem cells can effectively differentiate into the cell type to which their cellular microenvironment belongs (Kovina and Khodarovich, 2011), which supports the possibility of tissue renewal on intravenous administration of stem cells (SCs) This could explain the effective healing by bone marrow (BM) transplantation of blood diseases, and of systemic diseases such as mucopolysaccharidosis, senile hearing loss, and bullous epidermolysis (Birkenmeier et al, 1991; Iwai et al, 2001; Corti et al, 2004; Willenbring et al, 2004; Wagner et al, 2010). It is desirable to develop this technique in older animals, because at an earlier age, when the body has a sufficiently large stock of stem cells, the effectiveness of other methods of cell damage elimination and life prolongation is high (Spaulding et al, 1997; Aon et al, 2016), and the risk of invasive interference is not great

Objectives

Methods

Results

Discussion

Conclusion