Mesenchymal stromal cells derived from various tissues: Biological, clinical and cryopreservation aspects

Abstract

Originally isolated from bone marrow, mesenchymal stromal cells (MSCs) have since been obtained from various fetal and post-natal tissues and are the focus of an increasing number of clinical trials. Because of their tremendous potential for cellular therapy, regenerative medicine and tissue engineering, it is desirable to cryopreserve and bank MSCs to increase their access and availability. A remarkable amount of research and resources have been expended towards optimizing the protocols, freezing media composition, cooling devices and storage containers, as well as developing good manufacturing practices in order to ensure that MSCs retain their therapeutic characteristics following cryopreservation and that they are safe for clinical use. Here, we first present an overview of the identification of MSCs, their tissue sources and the properties that render them suitable as a cellular therapeutic. Next, we discuss the responses of cells during freezing and focus on the traditional and novel approaches used to cryopreserve MSCs. We conclude that viable MSCs from diverse tissues can be recovered after cryopreservation using a variety of freezing protocols, cryoprotectants, storage periods and temperatures. However, alterations in certain functions of MSCs following cryopreservation warrant future investigations on the recovery of cells post-thaw followed by expansion of functional cells in order to achieve their full therapeutic potential.

Isolation and Cryopreservation of Animal Mesenchymal Stromal Cells

“…Several studies have shown that successful cryopreservation of cells in suspension needs suiciently high cooling rates to reach quickly low temperatures and avoid slow-cooling injury, but low enough cooling rates to decrease the formation of intracellular ice and avoid rapid-cooling injury [51]. The responses to cooling rates are cell-type speciic, as distinct cell types have diferent membrane permeability parameters.…”

Applications and optimization of cryopreservation technologies to cellular therapeutics

“…There have been several reports of mesenchymal stromal cells for expansion and cryopreservation for clinical applications, such as in graft versus host disease [60], but the product potency has come into question [61] and cryopreservation was one of the steps under scrutiny. Further detailed studies indicated a range of reversible and non-reversible effects of cryopreservation in mesenchymal stromal cells using slow cooling with a range of DMSO concentrations and cell pre-treatments [62]. Post-thaw culture for 24 h was found to be effective in reparation of many of the cryo-induced abnormalities.…”

Transportation of Mesenchymal Stem Cells for Clinical Applications

“…Cryoprotectants are classiied into permeating and non-permeating agents depending on their ability to cross the cell membrane [11,12]. The permeating cryoprotectants, such as dimethyl sulphoxide (DMSO), are used for clinical preservation and banking of MSCs for the treatment of graft-versus-host disease (GVHD) [13]. The International Stem Cell Initiative (ISCI) recommends the use of dry shippers involving liquid nitrogen (-196°C) for frozen stem cell transportation [2].…”