Influence of Hypothermic Storage Fluids on Mesenchymal Stem Cell Stability: A Comprehensive Review and Personal Experience

Abstract

Mesenchymal stem cells have generated a great deal of interest due to their potential use in regenerative medicine and tissue engineering. Examples illustrating their therapeutic value across various in vivo models are demonstrated in the literature. However, some clinical trials have not proved their therapeutic efficacy, showing that translation into clinical practice is considerably more difficult and discrepancies in clinical protocols can be a source of failure. Among the critical factors which play an important role in MSCs’ therapeutic efficiency are the method of preservation of the stem cell viability and various characteristics during their storage and transportation from the GMP production facility to the patient’s bedside. The cell storage medium should be considered a key factor stabilizing the environment and greatly influencing cell viability and potency and therefore the effectiveness of advanced therapy medicinal product (ATMP) based on MSCs. In this review, we summarize data from 826 publications concerning the effect of the most frequently used cell preservation solutions on MSC potential as cell-based therapeutic medicinal products.

When Origin Matters: Properties of Mesenchymal Stromal Cells From Different Sources for Clinical Translation in Kidney Disease

“…Also, autologous MSC therapies are predominant (62.5%) over allogeneic. Similar trends have been also observed in other studies ( 47 , 48 , 324 ). Interestingly, in renal pathologies, BM-MSCs have been mostly used in allogeneic settings (59.4%), while AT-MSCs have been used mostly in an autologous manner (80%) ( Figures 3E i–iii).…”

“…Cell expansion requires enzyme dissociation and cell subculture, and while the evaluation of the optimal cell confluence may vary among operators, a 70–80% confluence is recommended to be reached before detachment ( 323 ). In general, passage numbers from 1 to 5 are commonly used in clinical trials ( 48 , 324 ) and we have also found similar trends in our search ( Table 2 ). The use of low passage MSCs for therapy is currently preferred to higher passages due to the impact that extended passaging has in decreasing the cell proliferation rates and increasing senescence times ( 242 , 333 – 337 ).…”

“…For many years BM has been the predominant cell type in clinical trials for kidney disease ( Figure 3D ) and others ( 47 , 48 , 324 ). One of the main advantages of using BM-MSCs is the ability to use them in autologous settings without triggering anti-donor immunoreactions.…”

Processing and Ex Vivo Expansion of Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells for the Development of an Advanced Therapy Medicinal Product for use in Humans

“…Similar results were observed for AT-MSCs resuspended in Ringer lactate or Hypo Thermosol when compared to AT-MSCs resuspended in only 0.9% NaCl. Thus, the type of carrier solution used represents an important factor that influences the maintenance of stability of MSC-based medicinal products [47]. In our approach, AT-MSCs do not undergo a cryopreservation procedure (except for the preparation of reference samples of the final product) in relation to other investigators, who added a cryopreservation step to the manufacturing procedure, as summarized by Mazini et al [48].…”

Microneedle arrays integrated with living organisms for smart biomedical applications

“…Recently, cell-based therapies emerge as a fast-growing field, and present great potential in tissue/organ repairing/regeneration and cancer treatment 14 , 15 . However, traditional cell-based therapies are frequently compromised by low cell viability and immune rejection between hosts and the cells 83 , 84 . How to achieve precise and controllable delivery of target cells in a convenient manner remains challenging.…”