Gelatin positively regulates the immunosuppressive capabilitiesof adipose-derived mesenchymal stem cells

Abstract

IntroductionAdipose-derived mesenchymal stem cells (Ad-MSCs) are highly multipotent cells with a high potential for differentiation into multiple cell types (Vieira et al., 2010;Park et al., 2012;Mellor et al., 2015). Ad-MSCs produce various growth factors that contribute to injury healing and tissue regeneration (Salgado et al., 2010). The antiinflammatory, immunomodulatory, and antioxidant properties of mesenchymal stem cells (MSCs) make them desirable candidates for cell-based therapies (Soleymaninejadian et al., 2012).The usefulness of MSCs has been selectively enhanced by either manipulating the culture media composition (Langenbach and Handschel, 2013) or by gene transduction (Liu et al., 2015). Pretreatment with proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), and interleukin-6 (IL-6), enhances the immunosuppressive capacity of MSCs by upregulating the expression of indoleamine-2,3-dioxygenase (IDO), which inhibits the proliferation of lymphocytes (Hoogduijn et al., 2010). Gelatin sponges incorporating high amounts of β-tricalcium phosphate (β TCP) have been used to stimulate rat bone marrow MSC proliferation and osteogenic differentiation by stimulating higher alkaline phosphatase (AP) activity and osteocalcin expression (Takahashi et al., 2005). Similarly, a scaffold prepared by mixing chitosan with gelatin, β TCP, and hydroxyapatite (HA) has also been used to induce MSC adhesion, differentiation, and proliferation (Zhao et al., 2006).MSCs cultured in a hyperoxic environment have enhanced viability and paracrine therapeutic capabilities (Song et al., 2010), as well as increased expression of the naturally occurring antioxidant stanniocalcin-1 (SC-1), which prevents oxygen-induced bronchopulmonary dysplasia in rats (Waszak et al., 2012). HO-1, a potent antioxidant enzyme, can be induced in undifferentiated MSCs treated with hemin, which renders the MSCs more resistant to oxidative injury (Barbagallo et al., 2008). Osteogenic growth peptide (OGP) induces HO-1 expression in human bone marrow MSCs, which induces osteogenic differentiation as evidenced by elevated levels of bone morphogenic protein-2 (BMP-2) and osteonectin (Vanella et al., 2010(Vanella et al., , 2013. We have previously reported that gelatin-induced osteogenic cell sheets had active cell proliferation with abundant extracellular matrix and upregulation of osteogenic markers (Kim et al., 2016). In the present study, we evaluated the effects of gelatin on

Dissolvable Gelatin‐Based Microcarriers Generated through Droplet Microfluidics for Expansion and Culture of Mesenchymal Stromal Cells

“…[ 40 ] Current and nascent separation techniques include tangential flow filtrations (TFF), counterflow centrifugation elutriations (CCE), and dead‐end sieving; these require sophisticated equipment for such separation process. [ 42 ] Simpler membrane‐based filtration faces the disadvantage of clogging (cake formation) during the cell–particle separation step. [ 25 ] Membrane‐less separation approaches such as microfluidic‐based sorting have also been explored to separate cells from particles; [ 40 ] nevertheless, this additional cell–particle separation step is time‐consuming and can present contamination or dead volume (cell loss) risks with the incorporation of another microfluidic module into the cell manufacturing workflow.…”

“…Gelatin has also been demonstrated as a substrate for 2D monolayer culture, for which others have found that adipogenesis and osteogenesis differentiation were enhanced. [ 41,42 ] This suggested that gelatin is a suitable substrate for the growth of MSC while maintaining cell differentiation capacity and multipotency. Also, as gelatin has been demonstrated as a safe material for human exposure and consumption (at least as an edible), there is relatively low but to no risk in the delivery of any highly degraded gelatin with the therapeutics of cell suspension.…”

Intravenous Administration of Heat Shock-Treated MSCs Can Improve Neuroprotection and Neuroregeneration in Canine Spinal Cord Injury Model

“…In this experiment, the third passage of cells was used as an allograft. These cells had previously been identified as having multilineage differentiation capabilities [ 19 , 20 ].…”

Therapeutic Effects of Intravenous Injection of Fresh and Frozen Thawed HO-1-Overexpressed Ad-MSCs in Dogs with Acute Spinal Cord Injury

“…The third passage (P3) of Ad-MSCs was used in subsequent experiments [21]. These cells have been previously confirmed for their multiline differentiation capability [16, 22].…”