Small-animal blood exchange is an emerging approach for systemic aging research

Melod Mehdipour, Payam Amiri, Chao Liu, Jonalyn DeCastro, Cameron Kato, Colin M. Skinner, Michael J. Conboy, Kiana Aran, Irina M. Conboy

Published: 2022-08-18 DOI: 10.1038/s41596-022-00731-5

Small-animal blood exchange

Aging research

Heterochronic parabiosis

Invasive techniques

Mathematical modeling

AI 解读

Efficient and safe single-cell cloning of human pluripotent stem cells using the CEPT cocktail

Profiling native pulmonary basement membrane stiffness using atomic force microscopy

Genetic circuit design automation with Cello 2.0

Synthesis of siRNA nanoparticles to silence plaque-destabilizing gene in atherosclerotic lesional macrophages

Scalable dual-omics profiling with single-nucleus chromatin accessibility and mRNA expression sequencing 2 (SNARE-seq2)

A practical guide to scanning light-field microscopy with digital adaptive optics

Effective high-throughput isolation of fully human antibodies targeting infectious pathogens

Improved sampling and DNA extraction procedures for microbiome analysis in food-processing environments

MOF-derived nanoporous carbons with diverse tunable nanoarchitectures

Tutorial: a statistical genetics guide to identifying HLA alleles driving complex disease

查看全部

Sections

Figures

References

We describe a small-animal blood exchange approach developed for aging research as an alternative to heterochronic parabiosis or plasma injections. In parabiosis, animals are surgically coupled, which has several disadvantages, including difficulty contro
Introduction
Materials
Procedure 1: design and fabrication of the small-animal blood exchange device
Procedure 2
Procedure 3: blood exchange mathematical modeling
Troubleshooting
Timing
Anticipated results
- References
- References
References
ACKNOWLEDGMENTS

Villeda, S. A. et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 477, 90–96 (2011).
Villeda, S. A. et al. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat. Med. 20, 659–663 (2014).
Loffredo, F. S. et al. Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell 153, 828–839 (2013).
Conboy, I. M. et al. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433, 760–764 (2005).
Conboy, I. M. & Rando, T. A. Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches. Cell Cycle 11, 2260–2267 (2012).
Conboy, M. J., Conboy, I. M. & Rando, T. A. Heterochronic parabiosis: historical perspective and methodological considerations for studies of aging and longevity. Aging Cell. 12, 525–530 (2013).
Elabd, C. et al. Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration. Nat. Commun. 5, 4082 (2014).
Yousef, H. et al. Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM1. Nat. Med. 25, 988–1000 (2019).
Yousef, H. et al. Systemic attenuation of the TGF-β pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal. Oncotarget 6, 11959–11978 (2015).
Castellano, J. M. et al. Human umbilical cord plasma proteins revitalize hippocampal function in aged mice. Nature 544, 488–492 (2017).
Yousef, H. et al. Age-associated increase in BMP signaling inhibits hippocampal neurogenesis. Stem Cells 33, 1577–1588 (2015).
Yousef, H. et al. hESC-secreted proteins can be enriched for multiple regenerative therapies by heparin-binding. Aging 5, 357–372 (2013).
Carlson, M. E. et al. Relative roles of TGF- β1 and Wnt in the systemic regulation and aging of satellite cell responses. Aging Cell 8, 676–689 (2009).
Carlson, M. E., Silva, H. S. & Conboy, I. M. Aging of signal transduction pathways, and pathology. Exp. Cell Res. 314, 1951–1961 (2008).
Egerman, M. A. et al. GDF11 Increases with age and inhibits skeletal muscle regeneration. Cell Metab. 22, 164–174 (2015).
Smith, L. K. et al. β2-Microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis. Nat. Med. 21, 932–937 (2015).
Conboy, I. M., Conboy, M. J. & Rebo, J. Systemic problems: a perspective on stem cell aging and rejuvenation. Aging 7, 754–765 (2015).
Schaffer, D. V. & Gage, F. H. Neurogenesis and neuroadaptation. Neuromol. Med. 5, 1–9 (2004).
Bruel-Jungerman, E., Laroche, S. & Rampon, C. New neurons in the dentate gyrus are involved in the expression of enhanced long-term memory following environmental enrichment. Eur. J. Neurosci. 21, 513–521 (2005).
Mehdipour, M. et al. Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline–albumin. Aging 12, 8790–8819 (2020).
Mehdipour, M. et al. Plasma dilution improves cognition and attenuates neuroinflammation in old mice. Geroscience http://doi.org/10.1007/s11357-020-00297-8 (2020).
Rebo, J. et al. A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood. Nat. Commun. 7, 13363 (2016).
Esser, F., Masselter, T. & Speck, T. Silent pumpers: a comparative topical overview of the peristaltic pumping principle in living nature, engineering, and biomimetics. Adv. Intell. Syst. 1, 1900009 (2019).
Horobin, J. T., Sabapathy, S. & Simmonds, M. J. Repetitive supra-physiological shear stress impairs red blood cell deformability and induces hemolysis. Artif. Organs 41, 1017–1025 (2017).
Zhang, T. et al. Study of flow-induced hemolysis using novel couette-type blood-shearing devices. Artif. Organs 35, 1180–1186 (2011).
Finerty, J. C. & Panos, T. C. Parabiosis intoxication. Proc. Soc. Exp. Biol. Med. 76, 833–835 (1951).
Finerty, J. C. Parabiosis in physiological studies. Physiol. Rev. 32, 277–302 (1952).
Horowitz, A. M. et al. Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain. Science 369, 167–173 (2020).
De Miguel, Z. et al. Exercise plasma boosts memory and dampens brain inflammation via clusterin. Nature (2021) http://doi.org/10.1038/s41586-021-04183-x
Zhang, G., Budker, V. & Wolff, J. A. High levels of foreign gene expression in hepatocytes after tail vein injections of naked plasmid DNA. Hum. Gene Ther. 10, 1735–1737 (1999).
McKeen, L. W. Introduction to fatigue of plastics and elastomers. Fatigue and Tribological Properties of Plastics and Elastomers 3rd edn (Elsevier, 2016); http://doi.org/10.1016/B978-0-323-44201-5.00001-0
McKeen, L. W. Introduction to the tribology of plastics and elastomers. Fatigue and Tribological Properties of Plastics and Elastomers 3rd edn (Elsevier, 2016); http://doi.org/10.1016/B978-0-323-44201-5.00002-2
Ventola, C. L. Medical applications for 3D printing: current and projected uses. P&T 39, 704–711 (2014).
Mastellos, D. C., Reis, E. S., Ricklin, D., Smith, R. J. & Lambris, J. D. Complement C3-targeted therapy: replacing long-held assertions with evidence-based discovery. Trends Immunol. 38, 383–394 (2017).
Ricklin, D., Hajishengallis, G., Yang, K. & Lambris, J. D. Complement: a key system for immune surveillance and homeostasis. Nat. Immunol. 11, 785–797 (2010).
Kolev, M., Le Friec, G. & Kemper, C. Complement—tapping into new sites and effector systems. Nat. Rev. Immunol. 14, 811–820 (2014).
Hajishengallis, G. & Lambris, J. D. Microbial manipulation of receptor crosstalk in innate immunity. Nat. Rev. Immunol. 11, 187–200 (2011).
Cardoso, A. L. et al. Towards frailty biomarkers: candidates from genes and pathways regulated in aging and age-related diseases. Ageing Res. Rev. 47, 214–277 (2018).
Niyonzima, N. et al. Complement activation by cholesterol crystals triggers a subsequent cytokine response. Mol. Immunol. 84, 43–50 (2017).
Björk, I. & Lindahl, U. Mechanism of the anticoagulant action of heparin. Mol. Cell. Biochem. 48, 161–182 (1982).
Chuang, Y.-J., Swanson, R., Raja, S. M. & Olson, S. T. Heparin enhances the specificity of antithrombin for thrombin and factor Xa independent of the reactive center loop sequence: evidence for an exosite determinant of factor Xa specificity in heparin-activated antithrombin. J. Biol. Chem. 276, 14961–14971 (2001).
Weitz, J. I. New anticoagulants for treatment of venous thromboembolism. Circulation 110, I-19–I-26 (2004).

Small-animal blood exchange is an emerging approach for systemic aging research

Extended

Extended Data Fig. 1 Overview and detailed parts and schematics of single-pump small-animal blood exchange device.

Supplementary information

Supplementary Information

推荐阅读