Abstract
In regenerative medicine, mesenchymal stem cells (MSCs) have shown their importance and potential in tissue reconstruction and immune system modification. However, such cells' potential is often diminished by factors such as oxidative stress, immune rejection, and inadequate engraftment. This review highlights the role of molecular hydrogen (H(2)) and cold atmospheric plasma (CAP) as adjunct therapies to improve the effectiveness of MSC therapy. H(2) has strong antioxidative and anti-inflammatory actions as it quenches reactive oxygen species and positively stimulates the Nrf2 pathway that promotes MSC survival and life. CAP, being a modulated source of ROS and RNS, also assists MSCs by altering the cellular redox balance, thus facilitating cellular adaptation, migration, and differentiation. H(2) and CAP in conjunction with each other assist in establishing an ambience favorable for promoting MSCs' survival and growth abilities, and reduce the healing time in various pathways such as wound, neuroprotection, and ischemia. Besides these concerns, this review also covers the best administration routes and doses of H(2) and CAP together with MSCs in therapy. This study informs on a novel dual method aimed at improving the outcome of MSC therapy while adding several molecular targets and relevant clinical uses concerning these therapies. Research of the future has to deal with bettering these protocols so that the therapeutic benefits can be maximized without long-term implications for clinical applications.