An In Vitro and In Vivo Comparison of Osteogenic Differentiation of Human Mesenchymal Stromal/Stem Cells

Abstract

The use of stem cells in regenerative medicine, including tissue engineering and transplantation, has generated a great deal of enthusiasm. Mesenchymal stromal/stem cells (MSCs) can be isolated from various tissues, most commonly, bone marrow but more recently adipose tissue, dental pulp, and Wharton’s jelly, to name a few. MSCs display varying phenotypic profiles and osteogenic differentiating capacity depending and their site of origin. MSCs have been successfully differentiated into osteoblasts both in vitro an in vivo but discrepancies exist when the two are compared: what happens in vitro does not necessarily happen in vivo, and it is therefore important to understand why these differences occur. The osteogenic process is a complex network of transcription factors, stimulators, inhibitors, proteins, etc., and in vivo experiments are helpful in evaluating the various aspects of this osteogenic process without distractions and confounding variables. With that in mind, the results of in vitro experiments need to be carefully considered and interpreted with caution as they do not perfectly replicate the conditions found within living organisms. This is where in vivo experiments help us better understand interactions that might occur in the osteogenic process that cannot be replicated in vitro. Potentially, these differences could also be exploited to develop an optimal MSC cell therapeutic product that can be used for bone disorders. There are many bone disorders, most of which cause a great deal of discomfort. Clinically acceptable protocols could be developed in which MSCs are used to aid in bone regeneration providing relief for patients with chronic pain. The aim of this review is to examine the differences between studies conducted in vitro and in vivo with regard to the osteogenic process to better define the gaps in current osteogenic research. By better understanding osteogenic differentiation, we can better define treatment strategies for various bone disorders.

A Comparative In Vitro and In Vivo Study of Osteogenicity by Using Two Biomaterials and Two Human Mesenchymal Stem Cell Subtypes

“…It should however be pointed out that the in vivo study is not as exhaustive as the in vitro study when bone-specific proteins and minerals are considered. In addition, as highlighted in a review article describing the osteogenic differentiation of human MSCs, the modifications observed in vitro are not always translated when the cells are grafted in an animal ( Mollentze et al, 2021 ).…”

Tuning the resorption-formation balance in anin vitro3D osteoblast-osteoclast co-culture model of bone

“…Future research should focus on validating [67] and refining the herein presented 3D co-culture model and three media to better reflect specific states of health and disease [68], and make it applicable to accept varying cell yields and cells with varying (osteoclastic) activity. One way to validate the model could be to use cells from a single patient and investigate the predictive capacity of the model by verifying if their cells in vitro respond similarly to those in vivo [66] when exposed to for example treatment options for osteoporosis such as bisphosphonates. For using such a model as a predictive tool in a clinical setting it would have to be developed into a faster, lower-maintenance and higher-throughput tool, because the time, effort and cost at this point make it unsuitable for routine clinical prediction [69].…”

“…While the current study focused primarily on mineralized matrix remodeling and the role of OC therein, OBs were only investigated to a lesser extent and osteocytes were omitted completely. Finally, the model has not been validated by comparison with the in vivo situation [66]. Future research should focus on validating [67] and refining the herein presented 3D co-culture model and three media to better reflect specific states of health and disease [68], and make it applicable to accept varying cell yields and cells with varying (osteoclastic) activity.…”

“…While the current study focused primarily on mineralized matrix remodeling and the role of OC therein, OBs were only investigated to a lesser extent and osteocytes were omitted completely. Finally, the model has not been validated by comparison with the in vivo situation [66].…”

Prodigious therapeutic effects of combining mesenchymal stem cells with magnetic nanoparticles

“…Despite the numerous studies that highlighted the therapeutic efficiency of MSCs, many serious obstacles encumber the shift of MSCs from bench to bedside and delay their presence in the treatment guidelines[ 8 ]. The most reported post-transplantation challenges that researchers bump into when they use MSCs in clinical studies: (1) The disparities in the differentiation potential between in vitro and in vivo [ 9 ]; (2) The shift in their immunological characteristics and cytokines secretion profile under different stress microenvironments that may exist at the site of injury mainly Hypoxia and inflammation[ 5 ]; (3) The poor homing and migratory abilities of administered MSCs which may vary based on the route of injection and microenvironment status[ 10 ]; and (4) The loss of signal emitted from labelled cells due to the leakage of contrast agent after being injected, leads to difficulties in tracking and monitoring of these cells[ 11 ].…”