Red blood cells
The carriers of the oxygen
Credit: Art by Nelli Aghekyan. Set in motion by Dr. Emanuele Petretto. Words by Dr. Suruchi Poddar. Project Coordinator: Dr. Masia Maksymowicz. Series Director: Dr. Radhika Patnala
#Extraordinarycelltypes #sciart #lifescience
Voyage of Little Red Riding Hood
Very similar to Little Red Riding Hood who liked talking to people on the way to her grandmother’s place, red blood cells also meet a lot of different cell types on their journey to deliver oxygen to tissues of the human body. Red blood cells (RBCs) start their journey from their origin in the bone marrow and end in the spleen, liver, and bone marrow where they are engulfed by the macrophages (1). The spleen is particularly referred to as the graveyard of RBCs because of its primary function of removing old, defective or dead RBCs (2).
RBCs, also known as erythrocytes, derive their name from a glycoprotein erythropoietin (EPO) which is secreted by the kidney in hypoxic (low oxygen levels) conditions (3). The release of EPO stimulates the production of red blood cells in the bone marrow by a process known as erythropoiesis. RBCs form nearly 99% of the cellular component of the blood (4). The purpose of RBCs is to transport oxygen from pulmonary capillaries to tissue capillaries.
After their formation in the bone marrow, RBCs proceed towards the heart via capillaries and enter it in a deoxygenated state from the vena cava (the largest vein that carries deoxygenated blood to the heart from different parts of the body). In the heart, RBCs are pushed through atriums and ventricles to find their way out of the heart through the semilunar valves (valves that regulate blood flow within the heart). After that, they reach the lungs via the pulmonary artery to pick up oxygen and turn the deoxygenated blood into an oxygenated state. RBCs then re-enter the heart via the pulmonary vein and are finally pushed out of the heart through the semilunar valves into the aorta (the largest artery of the body that carries oxygenated blood from the heart to the body). Descending through the aorta RBCs deliver oxygenated blood to the abdominal organs and lower limbs of the body. The whole process might seem like a lot, but it actually takes less than a minute for RBCs to circulate the entire body and return to the heart (5)!
The colour of life
Blood is the fluid of life because it feeds every cell of the human body by transporting oxygen and other nutrients necessary for its proper functioning. Red blood cells contain a protein called hemoglobin which gives them their characteristic bright red color. The respiratory pigment hemoglobin consists of four heme groups with an iron atom in the middle (6). The iron in the heme binds with oxygen and absorbs blue-green light, thus reflecting red-orange light and appearing red to the human eye. Amazingly, the heme groups fold in a completely different way when the iron atoms in them are bound to oxygen molecules. This changes their slouching dome shape structure to a distended flat disc shape therefore appearing bright red from dull red. This also explains why the oxygenated blood seems to be a different colour than the deoxygenated blood. It is convenient for oxygen to interact with transition metals, such as iron or copper, because of the ease of sharing electrons. As a result, electrons can easily bind to the iron in the heme group in an oxygenated state as well as let go of the iron in a deoxygenated state. Interestingly, there are many colours of blood. Depending on the type of respiratory pigment an animal contains, the colour of the blood can change significantly from blue to green to clear. For example, crabs have blue blood, an ice fish from Antarctica has clear blood and the blood of earthworms is green (7).
Lab-grown red blood cells
In this fast-moving and dynamic world, development and evolution are inevitable. From dairy to diamond and from brain to burger, everything is being grown in the lab nowadays, so why not blood? Yes, the answer to that question is the RESTORE trial. RESTORE — Recovery and Survival of Stem Cell Originated Red Cells, is an initiative by the NHS Blood and Transplant, University of Bristol, National Institute for Health and Care Research Cambridge Clinical Facility, in association with several other partner organizations (8). The goal of this pioneering clinical trial is to produce lab-grown red blood cells from the stem cells of the donor and perform a mini-transfusion of up to two teaspoons (about 10 mL) in the same donor. The aim of the transfusion is to compare the longevity and efficacy of the blood produced in a laboratory environment and the regular blood of the donor based on the hypothesis that fabricated brand new RBCs will have a longer survival period in the circulation and better performance than the standard donor RBCs (9). Anemia, thalassemia, sickle cell disease are amongst the many blood diseases that require regular long-term blood transfusions. Till date, there is no definite cure available for the genetic blood disorders/hemoglobinopathies (defects in the production of hemoglobin) except a bone marrow transplant which is not performed very often because of the significant risks involved (10). Therefore, it will be worth having a superior quality of blood available on demand which is capable of reducing the frequency of transfusion. It will also be helpful in generating rare blood types and minimizing the chances of triggering an immune response against donor blood cells during blood transfusion (11).
Recognizing and appreciating the labs working in this space
- Red Cell Laboratory, Sanguine Research. Amsterdam, Netherlands. https://www.sanquin.org/research/group-leader-overview/red-cell-laboratory/index
- Red Cell Centre — Molecular Diagnostics Laboratory, Synnovis. London, UK. https://www.synnovis.co.uk/departments-and-laboratories/red-cell-centre-molecular-diagnostics-laboratory
- Red Cell Disorders Laboratory, University of Washington. Seattle, Washington, USA. https://testguide.labmed.uw.edu/guideline/red_cell_disorders Twitter: @UWMedicine
- The Peters Lab, The Jackson Laboratory. Bar Harbor, Maine, US. https://www.jax.org/research-and-faculty/research-labs/the-peters-lab# Twitter: @jacksonlab
- The Red Blood Cell Laboratory, University of California San Francisco. San Francisco, California, US. https://rbclab.ucsf.edu/
- Bristol BioDesign Institute, University of Bristol. Bristol, England, UK. https://www.bristol.ac.uk/research/impact/stories/red-blood-cells/ ; Twitter: @BristolUni
- Sankaran Lab, Harvard Stem Cell Institute, Harvard University. Cambridge, Massachusetts, US. https://www.bloodgenes.org/ ; Twitter: @harvardstemcell
- Bonnet Lab, The Francis Crick Institute. London, UK. https://www.crick.ac.uk/research/labs/dominique-bonnet ; Twitter: @TheCrick
- Duraisingh Lab, Harvard School of Public Health, Harvard University. Boston, Massachusetts, US. https://www.hsph.harvard.edu/duraisingh-lab/
- Red Cell Haematology, King’s College London. London, UK. https://www.kcl.ac.uk/research/red-cell-haematology ; Twitter: @KingsCollegeLon
References
- Thiagarajan, Perumal et al. “How Do Red Blood Cells Die?.” Frontiers in physiology vol. 12 655393. 15 Mar. 2021, doi:10.3389/fphys.2021.655393
- Mebius, Reina E, and Georg Kraal. “Structure and function of the spleen.” Nature reviews. Immunology vol. 5,8 (2005): 606–16. doi:10.1038/nri1669
- Bhoopalan, Senthil Velan et al. “Erythropoietin regulation of red blood cell production: from bench to bedside and back.” F1000Research vol. 9 F1000 Faculty Rev-1153. 18 Sep. 2020, doi:10.12688/f1000research.26648.1
- K. Lew, in Comprehensive Sampling and Sample Preparation (Ed.: J. Pawliszyn), Academic Press: Oxford, 2012, pp 95.
- The Journey of a Red Blood Cell | Lorne Laboratories UK. Lorne Laboratories Ltd. https://www.lornelabs.com/news-events/blog/the-journey-of-a-red-blood-cell (accessed March 30, 2024).
- Schechter, Alan N. “Hemoglobin research and the origins of molecular medicine.” Blood vol. 112,10 (2008): 3927–38. doi:10.1182/blood-2008–04–078188.
- Lutz, Diana. “The Many Colors of Blood.” ChemMatters (2010). American Chemical Society. https://teachchemistry.org/chemmatters/february-2010/the-many-colors-of-blood (accessed April 2, 2024).
- U. of Bristol, RESTORE clinical trial. https://www.bristol.ac.uk/btru/work/trial/ (accessed April 3, 2024).
- Kutikuppala, Lakshmi Venkata Simhachalam et al. “Transfusions with laboratory-grown red blood cells: a new development in science.” Experimental hematology vol. 119–120 (2023): 1–2. doi:10.1016/j.exphem.2023.01.004
- Marengo-Rowe, Alain J. “The thalassemias and related disorders.” Proceedings (Baylor University. Medical Center) vol. 20,1 (2007): 27–31. doi:10.1080/08998280.2007.11928230
- Kale, Sampreeti Sri Sai et al. “Breakthrough in the scientific world: Lab-grown red blood cells used in transfusions.” Asian journal of transfusion science vol. 17,1 (2023): 143–144. doi:10.4103/ajts.ajts_148_22
About the author:
DR. SURUCHI PODDAR
Content Editor The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Poddar received a PhD in Biomedical Engineering from Indian Institute of Technology-Banaras Hindu University (IIT-BHU), Varanasi, India. She started her career as a postdoctoral researcher in 2020 with the Nanoscience Technology Center at the University of Central Florida, Orlando where she worked on a multi-organ human-on-a-chip system. Currently she is working on solid-state nanopore technology at Wake Forest University, North Carolina. When not working, she enjoys watching movies, cooking food and exploring new places, restaurants, attractions.
About the artist:
NELLY AGHEKYAN
Contributing Artist The League of Extraordinary Cell Types, Sci-Illustrate Stories
Nelli Aghekyan did a bachelor’s and master’s in Architecture in Armenia, after studying architecture and interior design for 6 years, she concentrated on her drawing skills and continued her path in the illustration world. She works mainly on children’s book illustrations, some of her books are now being published. Currently living in Italy, she works as a full-time freelance artist, collaborating with different companies and clients.
About the animator:
DR. EMANUELE PETRETTO
Animator The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Petretto received his Ph.D. in Biochemistry at the University of Fribourg, Switzerland, focusing on the behavior of matter at nanoscopic scales and the stability of colloidal systems. Using molecular dynamics simulations, he explored the delicate interaction among particles, interfaces, and solvents.
Currently, he is fully pursuing another delicate interaction: the intricate interplay between art and science. Through data visualization, motion design, and games, he wants to show the wonders of the complexity surrounding us.
About the series:
The League of Extraordinary Cell types
The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types in our body, that make our hearts tick ❤.
