Mesenchymal Stem Cell: History
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Subjects: Cell Biology
Contributor:
Ilona Kalaszczynska

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.

  • mesenchymal stem cells
  • cell therapy
  • preservation solutions
  • storage media
  • cell viability
  • quality control

1. Introduction

Mesenchymal stem cells or mesenchymal stromal cells (MSCs) are non-hematopoietic, multipotent stem cells that upon stimulation can differentiate into cells of mesodermal, ectodermal, or endodermal lineages [1][2][3][4]. Tri-lineage differentiation potential (osteogenic, chondrogenic and adipogenic), together with the ability to adhere to culture surfaces under standard culture conditions, expression of CD73, CD90, and CD105, and absence of CD45, CD34, CD14, or CD11b, CD79α or CD19, and HLA-DR surface antigens, are part of the standard criteria defining MSCs as set out by the International Society of Cellular Therapy (ISCT) [5]. Discovered initially in the bone marrow [6][7], MSCs may also be isolated from other tissues, e.g., adipose [8], extra-embryonic structures [9][10], or dental tissues [11].

Mesenchymal stem cells have important properties from the perspective of their applicability as medicinal products [12][13]. In the recent past, the dominant hypothesis was that the healing properties of MSCs result from their direct incorporation into the tissue. However, several studies demonstrated that the rate of MSC survival and engraftment seems to be low and transient, and may not explain the therapeutic results achieved by MSCs [14]. On the other hand, other reports confirmed that the regenerative and immunoregulatory activity of MSCs relies on trophic factors that they secrete, including MSC-derived extracellular vesicles (EVs or MSC-EVs), which stimulate resident cells to undertake physiological regenerative processes [15][16][17].

MSCs secrete a variety of proangiogenic, chemotactic, anti-apoptotic, anti-inflammatory, immunomodulating and remodeling soluble factors—platelet-derived growth factor-B (PDGFB), vascular endothelial factor (VEGF), angiopoietin-1 (Ang1), chemokine (C-X-C) ligand (CXCL2, CXCL12), chemokine (C-C) ligand (CCL2, CCL5), interleukin-1 receptor antagonist (IL-1Ra), transforming growth factor beta (TGF-β), stromal-derived factor-1 (SDF1), indoleamine 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2), matrix metalloproteinase-9 (MMP-9), and others [16][18][19].

Due to the properties described above, MSCs may seem to be “doomed to succeed”. However, most of the MSC-based therapies did not progress beyond preclinical or early clinical studies. There is an ongoing debate on the reasons why non-optimal clinical outcomes have been achieved [20][21]. Among others, the following factors could determine the effectiveness of MSCs: (1) the origin of source tissue [22]; (2) donor-to-donor [23], cell-to-cell [24], and passage-to-passage [25] variability; (3) various isolation and expansion methods including different oxygen levels [26] and culture medium composition [27], passage number, [28] preservation method; (4) route of delivery [29] and the number of cells administered [30]; and (5) health condition of the recipient. In an elegant review, Levy and Kuai et al. tackled each of the identified barriers to the implementation of MSC-based therapies [31]. It was shown that problems with diversity in the manufacturing and quality control of MSC-based medicinal products, as described by Mendicino et al., have still not been solved [32]. This applies to tissue sourcing, propagation methods, and in vitro and in vivo product characterization described in investigational new drug (IND) submissions to the U.S. FDA for MSC-based products.

A striking example illustrating the influence of different isolation, culture, and cryopreservation methods was demonstrated by Stroncek et al. in an experiment in which MSCs were manufactured from the same source material [33]. The authors pointed out that “manufacturing of MSCs by five independent centers contributed more to MSC variability than did the source material of the bone marrow” used in the study.

All these differences may lead to significant variations in MSC efficacy and potency. A validated potency assay with defined acceptance criteria secures consistency of quality and ensures that the medicinal product delivered to the patient will bring about the expected results. Due to the nature of cell-based medicinal products (a wide range of mechanisms of action), there is no consensus on any potency assay for MSCs. For now, ISCT minimum criteria [5] and viability verification provide a basis for establishing the quality of MSCs before their therapeutic application. The disadvantage of the current phenotypic classification of MSCs is that the characterized population is heterogeneous and subpopulations with different proliferative and differentiation potential can be distinguished [34][35][36]. This heterogeneity results in non-uniform tri-lineage differentiation potential, as was demonstrated in clonal studies with less than 50% of bone marrow-derived MSC clones possessing the tri-lineage differentiation potential [37].

MSC identity and potency testing are likely to change as more research is conducted to better define properties of MSCs—for example, additional phenotypic criteria including STRO-1, TWIST-1, DERMO-1, GSTT1, CD271 [38][39][40][41], an in vitro model of IL-10 release from blood cells [42], and MSC-mediated inhibition of T-cell activation [43][44]. However, such assays for potency testing of MSCs are not part of routine quality control, and their applicability remains to be determined.

It turns out that the manufacturing and application of cell-based therapies create problems of a different nature from those which are characteristic of chemical or protein-based drugs. Understanding and taming these differences is important for the successful development of the cell-based product formula, its efficient and safe delivery, and application.

2. Mesenchymal Stem Cells' Fate between Manufacturer and Clinic

A distinctive feature of the cell-based medicinal product is its low stability over time, and the maintenance of stability is crucial for the safe and effective implementation of cell-based therapies, as a lot of time can pass between the release from the GMP facility and administration of the product. A significant number of in vitro studies show that cell storage conditions induce changes in cellular morphology, viability, and therapeutic properties [45][46][47]. Consequently, this may result in insufficient therapeutic potency of cell-based medicinal products with a substantially reduced number of live cells. As one of the studies illustrates, over 50% of human MSC-based products derived from the umbilical cord do not meet the criteria of sufficient stability, as their viability at the moment of implantation is below 70% [48].

Unfortunately, at the early stages of cell-based product development, little attention was paid to the ways and means of cell-based medicinal product biopreservation before their application. As for the temperature, it is clear that hypothermic preservation at 2–8 °C is the most reproducible and non-cell-destructive storage system, as it supports higher viability of cells in comparison to those stored at room temperature [49]. Furthermore, although it is certainly most convenient to thaw and directly inject, this practice does not seem to be optimal. Freshly harvested MSCs can be stored for about 6–8 h without affecting their viability and differentiation potential, whereas frozen-thawed cells can be maintained for a maximum of 2 h after thawing before disturbing their viability significantly [50]. There is evidence that MSCs need a recovery phase after cryopreservation, prior to injection, to allow for best in vivo survival and immunomodulatory and therapeutic properties [51][52]. As for the storage solutions, their influence has only recently been taken into consideration, and in addition to well-known crystalloid solutions, media dedicated to the storage of cells-based medicinal products have also appeared on the market.

During cell storage, several metabolic pathways may be affected and cause cell oedema, accumulation of hypoxanthine and xanthine oxidase as well as a breakdown of ion homeostasis due to cell membrane depolarization [53]. Even though MSCs are considered to be more resistant to osmotic and oxidative stresses compared to differentiated cells, vehicle solutions should minimize or prevent those damaging conditions. To reduce cold-induced ionic perturbation, storage media ionic balance needs to be similar to the intracellular milieu and minimize the decrease in cell viability over time [54]. Moreover, a desirable feature of cell storage fluids would be the possibility of their direct administration together with cells. Therefore, due to the lack of dedicated cell preservation solutions, well-known “solutions for infusion” were investigated as storage and transportation solutions for cell-based medicinal products. Their composition mimics human physiological plasma electrolyte concentrations, osmolality and pH, hence they are more similar to the external than internal milieu. Solutions for infusion (also known as intravenous fluids or solutions) are supplemental fluids used in intravenous therapy to restore or maintain normal fluid volume and electrolyte balance and contain compounds that are semipermeable to capillary membranes or freely permeable ions in defined concentrations and can be grouped into colloid or crystalloid solutions, respectively [55]. Albumin suspended in saline may be considered a standard colloidal solution for infusion; however, its limited availability and high cost lead to the implementation of other semisynthetic compounds, e.g., succinylated gelatin, urea-linked gelatin-polygeline, dextran solutions, or hydroxyethyl starch [55]. On the other hand, crystalloids are “balanced” or “physiologic” solutions with multiple different formulations that closely mimic electrolyte composition, osmolality, and pH of human plasma. Implementation of lactate, acetate, gluconate, or malate anions in these solutions provides their additional buffer capacity. Crystalloids are easy to manufacture, cheap and not allergenic, and therefore, compared to colloids, they are frequently used for replacement or maintenance fluid therapy [56]. Normal saline (0.9%), Ringer’s lactated solution and Hartmann’s solution may be considered as the most popular worldwide [57][58]. Furthermore, the novel generation of crystalloids (Ionosteril, Starofundin, Plasma-Lyte) are also implemented as storage solutions, since they more closely resemble human plasma composition [59].

Limited studies on optimization and validation of the transport/storage conditions are available. Normal saline (0.9% NaCl) or phosphate-buffered saline (PBS) are most frequently used; however, the storage time is limited to 6–12 h (own experience). Ringer’s lactated solution supplemented with 1% human serum albumin (HAS) seems to support the viability of Wharton′s jelly MSCs (WJ-MSC) above the 70% threshold for up to 36 h of hypothermic storage [60]. This combination of components seems to be superior to 0.9% NaCl, 5% dextrose, 5% dextrose in sodium chloride, Plasma-Lyte or 1–5% HAS [48]. Upon storage in the mentioned formulations, WJ-MSCs displayed progressive deterioration in viability and adhesion ability, but the immunophenotype and immunosuppressive and differentiation capacities were relatively unaffected. Interestingly, storage of bone marrow-derived MSCs (BM-MSC) in PBS for 24 h also exhibited osteogenic differentiation capability in vitro, as shown by the mineralized matrix formation and alkaline phosphatase activity when cultured in an osteogenic medium [61]. Similarly, BM stored in 4% HSA in 0.9% saline for 18 h showed adhesion to hydroxyapatite tricalcium phosphate osteoconductive biomaterial (HA/β-TCP 3D scaffold) and subsequent in vivo bone formation [62]. In all of the above studies, it was shown that storage at room temperature was conversely related to viability rates. The addition of 6-chromanol derivate (SUL-109) as a preservation agent that protects cells from hypothermia and rewarming damage without affecting their subsequent differentiation capacity seems an interesting solution [63].

This entry is adapted from the peer-reviewed paper 10.3390/cells10051043

References

  1. Ahmadi, N.; Razavi, S.; Kazemi, M.; Oryan, S. Stability of neural differentiation in human adipose derived stem cells by two induction protocols. Tissue Cell 2012, 44, 87–94.
  2. Al Battah, F.; De Kock, J.; Vanhaecke, T.; Rogiers, V. Current status of human adipose-derived stem cells: Differentiation into hepatocyte-like cells. Sci. World J. 2011, 11, 1568–1581.
  3. Jin, G.; Prabhakaran, M.P.; Ramakrishna, S. Stem cell differentiation to epidermal lineages on electrospun nanofibrous substrates for skin tissue engineering. Acta Biomater. 2011, 7, 3113–3122.
  4. Pittenger, M.F.; Mackay, A.M.; Beck, S.C.; Jaiswal, R.K.; Douglas, R.; Mosca, J.D.; Moorman, M.A.; Simonetti, D.W.; Craig, S.; Marshak, D.R. Multilineage potential of adult human mesenchymal stem cells. Science 1999, 284, 143–147.
  5. Dominici, M.; Le Blanc, K.; Mueller, I.; Slaper-Cortenbach, I.; Marini, F.; Krause, D.; Deans, R.; Keating, A.; Prockop, D.; Horwitz, E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006, 8, 315–317.
  6. Friedenstein, A.J.; Chailakhyan, R.K.; Latsinik, N.V.; Panasyuk, A.F.; Keiliss-Borok, I.V. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 1974, 17, 331–340.
  7. Friedenstein, A.J.; Piatetzky, S., II; Petrakova, K.V. Osteogenesis in transplants of bone marrow cells. J. Embryol. Exp. Morphol. 1966, 16, 381–390.
  8. Zuk, P.A.; Zhu, M.; Mizuno, H.; Huang, J.; Futrell, J.W.; Katz, A.J.; Benhaim, P.; Lorenz, H.P.; Hedrick, M.H. Multilineage cells from human adipose tissue: Implications for cell-based therapies. Tissue Eng. 2001, 7, 211–228.
  9. Mitchell, K.E.; Weiss, M.L.; Mitchell, B.M.; Martin, P.; Davis, D.; Morales, L.; Helwig, B.; Beerenstrauch, M.; Abou-Easa, K.; Hildreth, T.; et al. Matrix cells from Wharton’s jelly form neurons and glia. Stem Cells 2003, 21, 50–60.
  10. Fukuchi, Y.; Nakajima, H.; Sugiyama, D.; Hirose, I.; Kitamura, T.; Tsuji, K. Human placenta-derived cells have mesenchymal stem/progenitor cell potential. Stem Cells 2004, 22, 649–658.
  11. Gronthos, S.; Mankani, M.; Brahim, J.; Robey, P.G.; Shi, S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc. Natl. Acad. Sci. USA 2000, 97, 13625–13630.
  12. Marquez-Curtis, L.A.; Janowska-Wieczorek, A.; McGann, L.E.; Elliott, J.A. Mesenchymal stromal cells derived from various tissues: Biological, clinical and cryopreservation aspects. Cryobiology 2015, 71, 181–197.
  13. Pittenger, M.F.; Discher, D.E.; Peault, B.M.; Phinney, D.G.; Hare, J.M.; Caplan, A.I. Mesenchymal stem cell perspective: Cell biology to clinical progress. NPJ Regen. Med. 2019, 4, 22.
  14. Kean, T.J.; Lin, P.; Caplan, A.I.; Dennis, J.E. MSCs: Delivery Routes and Engraftment, Cell-Targeting Strategies, and Immune Modulation. Stem Cells Int. 2013, 2013, 732742.
  15. Caplan, A.I.; Dennis, J.E. Mesenchymal stem cells as trophic mediators. J. Cell. Biochem. 2006, 98, 1076–1084.
  16. Eleuteri, S.; Fierabracci, A. Insights into the Secretome of Mesenchymal Stem Cells and Its Potential Applications. Int. J. Mol. Sci. 2019, 20, 4597.
  17. Prockop, D.J.; Kota, D.J.; Bazhanov, N.; Reger, R.L. Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs). J. Cell. Mol. Med. 2010, 14, 2190–2199.
  18. Ahangar, P.; Mills, S.J.; Cowin, A.J. Mesenchymal Stem Cell Secretome as an Emerging Cell-Free Alternative for Improving Wound Repair. Int. J. Mol. Sci. 2020, 21, 7038.
  19. Wangler, S.; Kamali, A.; Wapp, C.; Wuertz-Kozak, K.; Hackel, S.; Fortes, C.; Benneker, L.M.; Haglund, L.; Richards, R.G.; Alini, M.; et al. Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: A proteomic analysis. Stem Cell Res. Ther. 2021, 12, 11.
  20. Kabat, M.; Bobkov, I.; Kumar, S.; Grumet, M. Trends in mesenchymal stem cell clinical trials 2004–2018: Is efficacy optimal in a narrow dose range? Stem Cells Transl. Med. 2020, 9, 17–27.
  21. Prockop, D.J.; Prockop, S.E.; Bertoncello, I. Are clinical trials with mesenchymal stem/progenitor cells too far ahead of the science? Lessons from experimental hematology. Stem Cells 2014, 32, 3055–3061.
  22. Xu, L.; Liu, Y.; Sun, Y.; Wang, B.; Xiong, Y.; Lin, W.; Wei, Q.; Wang, H.; He, W.; Wang, B.; et al. Tissue source determines the differentiation potentials of mesenchymal stem cells: A comparative study of human mesenchymal stem cells from bone marrow and adipose tissue. Stem Cell Res. Ther. 2017, 8, 275.
  23. Kang, I.; Lee, B.C.; Choi, S.W.; Lee, J.Y.; Kim, J.J.; Kim, B.E.; Kim, D.H.; Lee, S.E.; Shin, N.; Seo, Y.; et al. Donor-dependent variation of human umbilical cord blood mesenchymal stem cells in response to hypoxic preconditioning and amelioration of limb ischemia. Exp. Mol. Med. 2018, 50, 1–15.
  24. McLeod, C.M.; Mauck, R.L. On the origin and impact of mesenchymal stem cell heterogeneity: New insights and emerging tools for single cell analysis. Eur. Cell Mater. 2017, 34, 217–231.
  25. Capra, E.; Beretta, R.; Parazzi, V.; Vigano, M.; Lazzari, L.; Baldi, A.; Giordano, R. Changes in the proteomic profile of adipose tissue-derived mesenchymal stem cells during passages. Proteome Sci. 2012, 10, 46.
  26. Hu, C.; Li, L. Preconditioning influences mesenchymal stem cell properties in vitro and in vivo. J. Cell Mol. Med. 2018, 22, 1428–1442.
  27. Czapla, J.; Matuszczak, S.; Kulik, K.; Wisniewska, E.; Pilny, E.; Jarosz-Biej, M.; Smolarczyk, R.; Sirek, T.; Zembala, M.O.; Zembala, M.; et al. The effect of culture media on large-scale expansion and characteristic of adipose tissue-derived mesenchymal stromal cells. Stem Cell Res. Ther. 2019, 10, 235.
  28. Yang, Y.K.; Ogando, C.R.; Wang See, C.; Chang, T.Y.; Barabino, G.A. Changes in phenotype and differentiation potential of human mesenchymal stem cells aging in vitro. Stem Cell Res. Ther. 2018, 9, 131.
  29. Kanelidis, A.J.; Premer, C.; Lopez, J.; Balkan, W.; Hare, J.M. Route of Delivery Modulates the Efficacy of Mesenchymal Stem Cell Therapy for Myocardial Infarction: A Meta-Analysis of Preclinical Studies and Clinical Trials. Circ. Res. 2017, 120, 1139–1150.
  30. Golpanian, S.; Schulman, I.H.; Ebert, R.F.; Heldman, A.W.; DiFede, D.L.; Yang, P.C.; Wu, J.C.; Bolli, R.; Perin, E.C.; Moye, L.; et al. Concise Review: Review and Perspective of Cell Dosage and Routes of Administration From Preclinical and Clinical Studies of Stem Cell Therapy for Heart Disease. Stem Cells Transl. Med. 2016, 5, 186–191.
  31. Levy, O.; Kuai, R.; Siren, E.M.J.; Bhere, D.; Milton, Y.; Nissar, N.; De Biasio, M.; Heinelt, M.; Reeve, B.; Abdi, R.; et al. Shattering barriers toward clinically meaningful MSC therapies. Sci. Adv. 2020, 6, eaba6884.
  32. Mendicino, M.; Bailey, A.M.; Wonnacott, K.; Puri, R.K.; Bauer, S.R. MSC-based product characterization for clinical trials: An FDA perspective. Cell Stem Cell 2014, 14, 141–145.
  33. Stroncek, D.F.; Jin, P.; McKenna, D.H.; Takanashi, M.; Fontaine, M.J.; Pati, S.; Schafer, R.; Peterson, E.; Benedetti, E.; Reems, J.A. Human Mesenchymal Stromal Cell (MSC) Characteristics Vary Among Laboratories When Manufactured From the Same Source Material: A Report by the Cellular Therapy Team of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Front. Cell Dev. Biol. 2020, 8, 458.
  34. Whitfield, M.J.; Lee, W.C.; Van Vliet, K.J. Onset of heterogeneity in culture-expanded bone marrow stromal cells. Stem Cell Res. 2013, 11, 1365–1377.
  35. Baer, P.C.; Kuci, S.; Krause, M.; Kuci, Z.; Zielen, S.; Geiger, H.; Bader, P.; Schubert, R. Comprehensive phenotypic characterization of human adipose-derived stromal/stem cells and their subsets by a high throughput technology. Stem Cells Dev. 2013, 22, 330–339.
  36. Russell, K.C.; Lacey, M.R.; Gilliam, J.K.; Tucker, H.A.; Phinney, D.G.; O’Connor, K.C. Clonal analysis of the proliferation potential of human bone marrow mesenchymal stem cells as a function of potency. Biotechnol. Bioeng. 2011, 108, 2716–2726.
  37. Muraglia, A.; Cancedda, R.; Quarto, R. Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. J. Cell Sci. 2000, 113 (Pt 7), 1161–1166.
  38. Samsonraj, R.M.; Rai, B.; Sathiyanathan, P.; Puan, K.J.; Rotzschke, O.; Hui, J.H.; Raghunath, M.; Stanton, L.W.; Nurcombe, V.; Cool, S.M. Establishing criteria for human mesenchymal stem cell potency. Stem Cells 2015, 33, 1878–1891.
  39. Boregowda, S.V.; Krishnappa, V.; Haga, C.L.; Ortiz, L.A.; Phinney, D.G. A Clinical Indications Prediction Scale Based on TWIST1 for Human Mesenchymal Stem Cells. EBioMedicine 2016, 4, 62–73.
  40. Sathiyanathan, P.; Samsonraj, R.M.; Tan, C.L.L.; Ling, L.; Lezhava, A.; Nurcombe, V.; Stanton, L.W.; Cool, S.M. A genomic biomarker that identifies human bone marrow-derived mesenchymal stem cells with high scalability. Stem Cells 2020, 38, 1124–1136.
  41. Buhring, H.J.; Battula, V.L.; Treml, S.; Schewe, B.; Kanz, L.; Vogel, W. Novel markers for the prospective isolation of human MSC. Ann. N. Y. Acad. Sci. 2007, 1106, 262–271.
  42. Jiao, J.; Milwid, J.M.; Yarmush, M.L.; Parekkadan, B. A mesenchymal stem cell potency assay. Methods Mol. Biol. 2011, 677, 221–231.
  43. Klinker, M.W.; Marklein, R.A.; Lo Surdo, J.L.; Wei, C.H.; Bauer, S.R. Morphological features of IFN-gamma-stimulated mesenchymal stromal cells predict overall immunosuppressive capacity. Proc. Natl. Acad. Sci. USA 2017, 114, E2598–E2607.
  44. Marklein, R.A.; Klinker, M.W.; Drake, K.A.; Polikowsky, H.G.; Lessey-Morillon, E.C.; Bauer, S.R. Morphological profiling using machine learning reveals emergent subpopulations of interferon-gamma-stimulated mesenchymal stromal cells that predict immunosuppression. Cytotherapy 2019, 21, 17–31.
  45. Petrenko, Y.; Chudickova, M.; Vackova, I.; Groh, T.; Kosnarova, E.; Cejkova, J.; Turnovcova, K.; Petrenko, A.; Sykova, E.; Kubinova, S. Clinically Relevant Solution for the Hypothermic Storage and Transportation of Human Multipotent Mesenchymal Stromal Cells. Stem Cells Int. 2019, 2019, 5909524.
  46. Pogozhykh, D.; Prokopyuk, V.; Pogozhykh, O.; Mueller, T.; Prokopyuk, O. Influence of Factors of Cryopreservation and Hypothermic Storage on Survival and Functional Parameters of Multipotent Stromal Cells of Placental Origin. PLoS ONE 2015, 10, e0139834.
  47. Robinson, N.J.; Picken, A.; Coopman, K. Low temperature cell pausing: An alternative short-term preservation method for use in cell therapies including stem cell applications. Biotechnol. Lett. 2014, 36, 201–209.
  48. Chen, Y.; Yu, B.; Xue, G.; Zhao, J.; Li, R.K.; Liu, Z.; Niu, B. Effects of storage solutions on the viability of human umbilical cord mesenchymal stem cells for transplantation. Cell Transplant. 2013, 22, 1075–1086.
  49. Gniadek, T.J.; Garritsen, H.S.P.; Stroncek, D.; Szczepiorkowski, Z.M.; McKenna, D.H.; on behalf of the Biomedical Excellence for Safer Transfusion Collaborative. Optimal Storage Conditions for Apheresis Research (OSCAR): A Biomedical Excellence for Safer Transfusion (BEST) Collaborative study. Transfusion 2018, 58, 461–469.
  50. Pal, R.; Hanwate, M.; Totey, S.M. Effect of holding time, temperature and different parenteral solutions on viability and functionality of adult bone marrow-derived mesenchymal stem cells before transplantation. J. Tissue Eng. Regen. Med. 2008, 2, 436–444.
  51. Francois, M.; Copland, I.B.; Yuan, S.; Romieu-Mourez, R.; Waller, E.K.; Galipeau, J. Cryopreserved mesenchymal stromal cells display impaired immunosuppressive properties as a result of heat-shock response and impaired interferon-gamma licensing. Cytotherapy 2012, 14, 147–152.
  52. Moll, G.; Alm, J.J.; Davies, L.C.; von Bahr, L.; Heldring, N.; Stenbeck-Funke, L.; Hamad, O.A.; Hinsch, R.; Ignatowicz, L.; Locke, M.; et al. Do cryopreserved mesenchymal stromal cells display impaired immunomodulatory and therapeutic properties? Stem Cells 2014, 32, 2430–2442.
  53. Guibert, E.E.; Petrenko, A.Y.; Balaban, C.L.; Somov, A.Y.; Rodriguez, J.V.; Fuller, B.J. Organ Preservation: Current Concepts and New Strategies for the Next Decade. Transfus. Med. Hemother. 2011, 38, 125–142.
  54. Abazari, A.; Hawkins, B.J.; Clarke, D.M.; Mathew, A.J. Biopreservation Best Practices: A Cornerstone in the Supply Chain of Cell-based Therapies—MSC Model Case Study. Cell Gene Ther. Insights 2017, 3, 853–871.
  55. Myburgh, J.A.; Mythen, M.G. Resuscitation fluids. N. Engl. J. Med. 2013, 369, 1243–1251.
  56. Weinberg, L.; Collins, N.; Van Mourik, K.; Tan, C.; Bellomo, R. Plasma-Lyte 148: A clinical review. World J. Crit. Care Med. 2016, 5, 235–250.
  57. Young, P.; Bailey, M.; Beasley, R.; Henderson, S.; Mackle, D.; McArthur, C.; McGuinness, S.; Mehrtens, J.; Myburgh, J.; Psirides, A.; et al. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial. JAMA 2015, 314, 1701–1710.
  58. Semler, M.W.; Self, W.H.; Wanderer, J.P.; Ehrenfeld, J.M.; Wang, L.; Byrne, D.W.; Stollings, J.L.; Kumar, A.B.; Hughes, C.G.; Hernandez, A.; et al. Balanced Crystalloids versus Saline in Critically Ill Adults. N. Engl. J. Med. 2018, 378, 829–839.
  59. Ripolles-Melchor, J.; Chappell, D.; Espinosa, A.; Mhyten, M.G.; Abad-Gurumeta, A.; Bergese, S.D.; Casans-Frances, R.; Calvo-Vecino, J.M. Perioperative fluid therapy recommendations for major abdominal surgery. Via RICA recommendations revisited. Part I: Physiological background. Rev. Esp. Anestesiol. Reanim. 2017, 64, 328–338.
  60. Celikkan, F.T.; Mungan, C.; Sucu, M.; Ulus, A.T.; Cinar, O.; Ili, E.G.; Can, A. Optimizing the transport and storage conditions of current Good Manufacturing Practice-grade human umbilical cord mesenchymal stromal cells for transplantation (HUC-HEART Trial). Cytotherapy 2019, 21, 64–75.
  61. Muraki, K.; Hirose, M.; Kotobuki, N.; Kato, Y.; Machida, H.; Takakura, Y.; Ohgushi, H. Assessment of viability and osteogenic ability of human mesenchymal stem cells after being stored in suspension for clinical transplantation. Tissue Eng. 2006, 12, 1711–1719.
  62. Veronesi, E.; Murgia, A.; Caselli, A.; Grisendi, G.; Piccinno, M.S.; Rasini, V.; Giordano, R.; Montemurro, T.; Bourin, P.; Sensebe, L.; et al. Transportation conditions for prompt use of ex vivo expanded and freshly harvested clinical-grade bone marrow mesenchymal stromal/stem cells for bone regeneration. Tissue Eng. Part C Methods 2014, 20, 239–251.
  63. Hajmousa, G.; Vogelaar, P.; Brouwer, L.A.; van der Graaf, A.C.; Henning, R.H.; Krenning, G. The 6-chromanol derivate SUL-109 enables prolonged hypothermic storage of adipose tissue-derived stem cells. Biomaterials 2017, 119, 43–52.
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