image: Figure 1. Proliferation of male and female BMECs increases with female MK CM treatment. (A) Male BMECs treated with male MK CM. (B) Female BMECs treated with female MK CM. (C) Female BMECs treated with male MK CM. (D) Male BMECs treated with female MK CM. The number of cells was quantified following a 48-hour incubation period. Data are expressed as a mean ± SD fold change relative to their respective controls (n = 3–11 biological replicates/group). For the negative control group (α-MEM lacking serum), n = 3 for male and 4 for female BMECs). Significance was determined using a one-way ANOVA with Tukey’s post-hoc test (A, B, D) or Kruskal-Wallis test (C) depending on the normalcy of the data distribution as determined by a Shapiro-Wilk test. Female BMECs treated with young female MK CM, old female MK CM, and young male MK CM proliferated significantly more than control female BMECs. Male BMECs treated with young or old female MK CM exhibited significantly greater proliferation. No significant differences in proliferation were found in male BMECs treated with male MK CM.
Credit: © 2024 Nazzal et al.
“With aging, the risk of fractures and compromised healing increases.”
BUFFALO, NY- December 4, 2024 – A new research paper was published in Aging (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science) Volume 16, Issue 21 on November 22, 2024, entitled, “The effects of young and aged, male and female megakaryocyte conditioned media on angiogenic properties of endothelial cells.”
Researchers Murad K. Nazzal, Hanisha L. Battina, Nikhil P. Tewari, Sarah L. Mostardo, Rohit U. Nagaraj, Donghui Zhou, Olatundun D. Awosanya, Saveda K. Majety, Sue Samson, Rachel J. Blosser, Ushashi C. Dadwal, Patrick L. Mulcrone, and Melissa A. Kacenaat from Indiana University School of Medicine and Richard L. Roudebush Veterans’ Administration Medical Center, have uncovered how certain bone marrow cells, called megakaryocytes (MKs), promote the growth of new blood vessels (angiogenesis) to aid in bone healing. Their findings help explain why healing slows with age and offer insights into potential treatments to accelerate fracture recovery in older adults.
Broken bones are common in older adults, and slower healing can lead to complications and longer hospital stays. Accelerating the healing process could significantly improve the quality of life for millions.
In this study, researchers investigated the effects of substances secreted by MKs, collected from young and older male and female mice. These substances, known as conditioned media (CM), were tested for their ability to stimulate the growth and function of endothelial cells (EC), which form the building blocks of blood vessels. Blood vessels play a critical role in healing by delivering oxygen and nutrients to damaged areas, making angiogenesis a vital part of the recovery process.
The results showed that CM from younger MKs mice was more effective at helping blood vessels grow. Interestingly, MKs from female mice performed better than those from males, regardless of age. For example, substances from female MKs mice boosted blood vessel growth by over 115% and significantly improved the movement of cells needed for healing.
The researchers also studied changes in genes related to blood vessel growth, and found that aging affects how these genes work. These changes may explain why older people heal more slowly after breaking a bone.
“An understanding of which factors regulate which mechanisms of EC functionality may allow for isolation of one or a few factors that influence EC migration changes with aging, resulting in the development of targeted therapy to improve EC migration, subsequent angiogenesis, and fracture healing.”
In conclusion, this research paves the way for developing new therapies to help older individuals recover from fractures more quickly, reducing pain and improving mobility. One potential approach could involve creating treatments that replicate the effects of MKs from younger individuals or isolating the specific substances that promote blood vessel growth. This represents an important step toward addressing the growing challenge of delayed healing in an aging population.
Read the full paper: DOI: https://doi.org/10.18632/aging.206077
Corresponding authors: Patrick L. Mulcrone – pamulcro@iu.edu, and Melissa A. Kacena – mkacena@iupui.edu
Keywords: aging, bone marrow endothelial cells, megakaryocyte, conditioned media, angiogenesis
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About Aging:
The journal Aging aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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Journal
Aging-US
Method of Research
News article
Subject of Research
Animals
Article Title
The effects of young and aged, male and female megakaryocyte conditioned media on angiogenic properties of endothelial cells
Article Publication Date
22-Nov-2024
COI Statement
The authors declare no conflicts of interest related to this study.