Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jul 26, 2023; 15(7): 701-712
Published online Jul 26, 2023. doi: 10.4252/wjsc.v15.i7.701
Commitment of human mesenchymal stromal cells to skeletal lineages is independent of their morphogenetic capacity
Jessica Cristina Marín-Llera, Damián García-García, Estefania Garay-Pacheco, Victor Adrian Cortes-Morales, Juan Jose Montesinos-Montesinos, Jesus Chimal-Monroy
Jessica Cristina Marín-Llera, Damián García-García, Estefania Garay-Pacheco, Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Coyoacan 04510, Mexico
Victor Adrian Cortes-Morales, Juan Jose Montesinos-Montesinos, Laboratorio de Células Troncales Mesenquimales, Unidad de Investigación Médica en Enfermedades Oncológicas, Hospital de Oncología Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico
Jesus Chimal-Monroy, Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Coyoacan 04510, Mexico
Author contributions: Marín-Llera JC and Chimal-Monroy J conceptualized the research and wrote the manuscript; Marín-Llera JC, Montesinos-Montesinos JJ, and Chimal-Monroy J discussed the data; Marín-Llera JC, García-García RD, and Garay-Pacheco E performed the experiments; Adrian Cortes-Morales V maintained and prepared the mesenchymal stromal cells; and all authors approved the final version of the manuscript.
Supported by the Dirección General de Asuntos del Personal Académico (DGAPA)-Universidad Nacional Autónoma de México, No. IN211117; Consejo Nacional de Ciencia y Tecnología (CONACyT), No. 1887 CONACyT-Fronteras de la Ciencia awarded to Chimal-Monroy J; García-García RD and Garay-Pacheco E received an undergraduate scholarship; and Marin-Llera JC a postdoctoral fellowship from the Consejo Nacional de Ciencia y Tecnología, No. CONACyT-Fronteras de la Ciencia-1887.
Institutional review board statement: The studies involving human cells were reviewed and approved by the Institutional Review Board for health research of the Instituto Mexicano del Seguro Social (IMSS, Mexico City, Mexico).
Institutional animal care and use committee statement: The handling protocol for the use of chicken embryos was done in embryonic stages in which the embryos do not feel pain because the nervous system development is not yet complete.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jesus Chimal-Monroy, PhD, Research Scientist, Senior Researcher, Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Apartado Postal 70228, Coyoacan 04510, Mexico. jchimal@unam.mx
Received: December 29, 2022
Peer-review started: December 29, 2022
First decision: April 27, 2023
Revised: May 18, 2023
Accepted: June 25, 2023
Article in press: June 25, 2023
Published online: July 26, 2023
Processing time: 208 Days and 3.2 Hours
ARTICLE HIGHLIGHTS
Research background

Mesenchymal stem cells (MSCs) differentiate in vitro to different skeletal lineages; however, it is unknown if they have the ability to form complex skeletal structures.

Research motivation

Although MSCs are considered relevant in regenerative medicine, reliable integration into adult tissues or de novo tissue formation has not been demonstrated. The application of MSCs in regenerative medicine needs to focus on understanding their biological characteristics to gain insights into how MSCs can integrate into adult tissues or properly rebuild tissues and organs.

Research objectives

To evaluate the ability of MSCs to organize and form complex skeletal structures in vivo under the influence of embryonic signals.

Research methods

The recombinant limb (RL) is an experimental system that recapitulates the embryonic environment and its influence on cells to generate skeletal structures. Here, umbilical cord blood (UCB)-MSCs or placenta (PL)-MSCs were placed in an RL to assess their ability to form skeletal structures. The evaluation was conducted by Alcian blue staining, immunofluorescence, and quantitative polymerase chain reaction of molecular markers of skeletal lineages.

Research results

MSCs expressed molecular markers of skeletal lineages but were unable to generate complex skeletal structures. PL-MSCs or UCB-MSCs integrated into an RL implanted in a chicken embryo. They responded differently to ectodermal signals starting the chondrogenic, osteogenic, or tenogenic program with high SRY-box transcription factor 9, Runt-related transcription factor 2, and scleraxis gene expression levels. However, PL-MSCs or UCB-MSCs did not complete the cell differentiation and morphogenetic processes, likely due to the intrinsic characteristics of MSCs.

Research conclusions

PL-MSCs or UCB-MSCs express molecular markers of skeletal lineages but do not organize into complex skeletal structures. The use of RLs is an excellent model for determining the ability of cells from other origins than limb bud mesodermal cells to generate skeletal structures. The inability of MSCs to form skeletal structures might be due to their intrinsic characteristics. Additional studies are needed to understand the properties of MSCs and whether they can integrate into adult tissues or properly rebuild tissues and organs.

Research perspectives

The application of MSCs to regenerative medicine needs to focus on understanding their biological characteristics to gain insights into how MSCs can integrate into adult tissues or properly rebuild tissues and organs.