Role of Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) in the Bone Regeneration: A Systematic Review from 2007-2018

Abstract

Background: The therapeutic value of mesenchymal stem cells (MSCs) in tissue engineering and regenerative medicine is attributable in part to paracrine pathways triggered by several secreted factors secreted into culture media. The secreted factor here is known as the conditioned medium (CM) or secretome.
 Objectives: This review is aimed to investigate and summarise the in-vitro, pre-clinical in-vivo studies regarding the role of CM-MSC in bone regeneration from 2007 until 2018
 Data Sources: A systematic literature search on PubMed, MEDLINE, OVID, Scopus and Cochrane library was carried out by using search terms: Secretome, conditioned medium, mesenchymal stem cell, bone healing, osteogenic, osteogenesis.
 Methods: A total of 611 articles were reviewed. Ten articles were identified as relevant for this systematic literature review.
 Results: Three tables of studies were constructed for in vitro studies and in-vivo studies.
 Conclusion: All of the included in-vitro studies and in-vivo studies have shown a promoting effect of bone regeneration at various stages. Although there are no clinical studies regarding the use of CM-MSC in the human bone regeneration that have been conducted, transplantation of secretome has shown a promising result in the acceleration of bone healing process.

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

“…They play an important role in maintenance of hematopoietic stem cell niche and are considered as a critical stem cell niche component in different tissues ( Kfoury and Scadden, 2015 ). Accumulating evidence indicated that MSC regenerative effects are mostly mediated by their ability to produce a wide range of bioactive molecules such as growth factors ( Chen et al, 2019 ; Dilogo and Fiolin, 2019 ; Seetharaman and Srivastava, 2019 ) and cytokines ( Selich et al, 2019 ), extracellular vesicles ( Keshtkar et al, 2018 ; Gowen et al, 2020 ) as well as ECM components ( Kalinina et al, 2015 ; Ragelle et al, 2017 ; Rolandsson Enes et al, 2017 ; Devaud et al, 2018 ). Extracellular matrix production by MSCs is enhanced if cells are cultured as cell sheets which can be used as cell-derived matrices after decellularization.…”

Mechanism of spinal cord injury regeneration and the effect of human neural stem cells-secretome treatment in rat model

“…The secretomes of stem cell help mitigate the risk of immune rejection, reduce the risk of tumorigenesis, and cryopreserve treatments while avoiding the issues of maintaining cell viability[ 9 ]. The secretomes of stem cell are more economical and readily available in emergency cases as they can be mass-produced[ 10 ].…”

The Role of Human Neural Stem Cell Secretomes on the Repair of Spinal Cord Injury Post-laminectomy in Rattus norvegicus Through the Analysis of Basso–Beattie–Bresnahan Score Locomotors, Interleukin-10, Matrix Metalloproteinase 9, and Transforming Growth Factor-β

“…Recently, researchers have mainly focused on therapies targeted at secondary cascade SCI [ 4 , 5 , 9 ]. Although the efficacy of stem cells as a neuroprotective agent is very promising, growing evidence has proven the efficacy of secretomes, which is supported more by the paracrine effects of the secretomes rather than the cells themselves [ 10 , 11 ], and after 14 days of stem cell injection in the tail vein of mice, only about 4% of the stem cells were present in the brain with 10% surviving [ 7 ]. Moreover, stem cell secretomes can reduce the negative impact of stem cells, including the possibility of malignancy [ 10 ].…”