. See, e.g., MCR 6.201(C)(2) (a trial court may review
materials otherwise protected by privilege in an in-camera
proceeding to determine if a defendant may have access to them
because they are "necessary to the defense").
[5] An open record has a separate
beneficial, if collateral, effect. When the parties are able to
dispute the facts of the case fully, then they help create a
complete record, facilitating appellate review. See generally Smith
v Crime Victims Compensation Bd, 130 Mich App 625, 628-629;
344 NW2d 23 (1983).if Yum raises the wage of its roughly 34k employees $1/hour, that’s roughly 275k/day or almost 2 million/week, 100 million a year. I’m not sure where the current hourly wage for their employees is, but if it’s the current min wage and bump to 15, that’s 2 million a day or 700 million a year. KFC, Pizza Hut, Taco Bell among others are going to be luxuries for sure. Especially when their suppliers also have to raise their food costs to accommodate labor increase also.
Edit- just saw they are only a 1.2 billion company, they are boned for sure.A comprehensive characterisation of large-scale expanded human bone marrow and umbilical cord mesenchymal stem cells

Background The manufacture of mesenchymal stem/stromal cells (MSCs) for clinical use needs to be cost effective, safe and scaled up. Current methods of expansion on tissue culture plastic are labour-intensive and involve several ‘open’ procedures. We have used the closed Quantum® hollow fibre bioreactor to expand four cultures each of MSCs derived from bone marrow (BM) and, for the first time, umbilical cords (UCs) and assessed extensive characterisation profiles for each, compared to parallel cultures grown on tissue culture plastic. Methods Bone marrow aspirate was directly loaded into the Quantum®, and cells were harvested and characterised at passage (P) 0. Bone marrow cells were re-seeded into the Quantum®, harvested and further characterised at P1. UC-MSCs were isolated enzymatically and cultured once on tissue culture plastic, before loading cells into the Quantum®, harvesting and characterising at P1. Quantum®-derived cultures were phenotyped in terms of immunoprofile, tri-lineage differentiation, response to inflammatory stimulus and telomere length, as were parallel cultures expanded on tissue culture plastic. Results Bone marrow cell harvests from the Quantum® were 23.1 ± 16.2 × 106 in 14 ± 2 days (P0) and 131 ± 84 × 106 BM-MSCs in 13 ± 1 days (P1), whereas UC-MSC harvests from the Quantum® were 168 ± 52 × 106 UC-MSCs after 7 ± 2 days (P1). Quantum®- and tissue culture plastic-expanded cultures at P1 adhered to criteria for MSCs in terms of cell surface markers, multipotency and plastic adherence, whereas the integrins, CD29, CD49c and CD51/61, were found to be elevated on Quantum®-expanded BM-MSCs. Rapid culture expansion in the Quantum® did not cause shortened telomeres when compared to cultures on tissue culture plastic. Immunomodulatory gene expression was variable between donors but showed that all MSCs upregulated indoleamine 2, 3-dioxygenase (IDO). Conclusions The results presented here demonstrate that the Quantum® can be used to expand large numbers of MSCs from bone marrow and umbilical cord tissues for next-generation large-scale manufacturing, without impacting on many of the properties that are characteristic of MSCs or potentially therapeutic. Using the Quantum®, we can obtain multiple MSC doses from a single manufacturing run to treat many patients. Together, our findings support the development of cheaper cell-based treatments. Electronic supplementary material The online version of this article (10.1186/s13287-019-1202-4) contains supplementary material, which is available to authorized users.


Introduction
Bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) were first described in 1968 [1] and were suggested to have multilineage potential in 1991 [2]. Since then, there has been huge interest in investigating the potential of these cells in the development of cell-based therapies. BM-MSCs have been shown to differentiate into bone, cartilage and fat lineages in vitro [3] and have been used clinically in orthopaedics and in other fields, most notably in the treatment of graft versus host disease (GvHD). Numerous tissue sources for the derivation of MSCs have been identified, including umbilical cord and adipose tissues [4,5].
The minimal criteria for MSC characterisation were first published in 2006 by the International Society for Cellular Therapy (ISCT) [6], which were subsequently amended for adipose-derived MSCs [7]. In recent years, there has been an increasing body of evidence from in vitro and in vivo studies suggesting that MSCs exert their therapeutic potency via trophic effects on endogenous cells as well as by the secretion of immunomodulatory molecules [8][9][10][11][12]. Further, it is well established that the ability of MSCs to modulate inflammatory processes is enhanced by their stimulation with pro-inflammatory cytokines (present in many disease states), such as tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interferon-γ (IFN-γ) [9,13]. A more recent statement paper was published by the ISCT in 2013 [9], which included detailed criteria for the immunomodulatory characteristics of MSCs. This working proposal advises that the characterisation of stem cells for therapy should include activation or 'licencing', which involves MSC culture stimulation with IFN-γ, either alone or with the addition of TNF-α [9].
MSCs derived from bone marrow and, more recently, umbilical cords (UC-MSCs) have been receiving increasing interest in the field of clinical orthopaedic regenerative medicine [14][15][16][17]. We have previously studied these MSC types separately and have compared the phenotypes of these cells in in vitro studies [5]. We are currently assessing BM-MSCs versus UC-MSCs in preclinical in vivo cartilage injury and osteoarthritis models. Autologous culture-expanded BM-MSCs are also being assessed in a randomised clinical trial for cartilage repair, comparing their efficacy versus the current cell therapy 'gold standard', autologous chondrocyte implantation (ACI), alone or in combination in the ASCOT trial [18]. BM-MSCs have been used clinically both in autologous [19] and in allogeneic transplantations [20,21], whereas UC-MSC therapies are being developed as an allogeneic treatment option [22]. Allogeneic cell therapies have many obvious advantages over autologous options as they can be developed as an 'off-the-shelf'therapy with one-step treatment and the ability to bank several doses from a single production run, thereby significantly reducing both manufacturing and treatment costs. Moreover, allogeneic cell therapies can be employed when autologous options are not suitable, for instance when autologous donor tissues such as bone marrow might not yield a biologically relevant cell mass, which is likely the case for extremely elderly orthopaedic patients.
There are several publications describing the best practice for the expansion and of the UC-MSC populations using traditional TCP techniques and for the cryogenic banking of UC-MSCs for allogeneic clinical use [23][24][25]. The good manufacturing practice (GMP) compliant Quantum® bioreactor, manufactured by Terumo BCT, has been used in several pre-clinical and clinical production runs for BM-MSCs and MSCs derived from adipose tissues [26][27][28][29][30][31][32][33][34][35][36], but to our knowledge has not been used to expand UC-MSCs. Sub-populations of cells (distinct in morphology to MSCs) have been described following the initial expansion phase of cells from the bone marrow [37], but these are poorly characterised. The bioreactor itself is made up of~11.5 × 10 3 polysulphone hollow fibres with semi-permeable membranes, which equates to a surface area of 2.1 m 2. Each fibre is approximately 215 μm in diameter and as such is only suitable for thin surface coatings and monolayers of adherent cells, rather than cell clusters and tissues. Monolayer cultures are monitored for growth by analysing media taken from a sample port to measure glucose and lactate concentrations, since these small molecules pass freely across the bioreactor membranes. The system has been shown to effectively scale-up MSC manufacturing, required for the switch from autologous to allogeneic manufacture and multi-dose banking [28,31]. The proliferative capacity of MSCs at low passage may be critical to forming useful cell banks since there are reports that BM-MSC at higher passage number (passage 5 to 10) may have diminished efficiency and reduced therapeutic effect in vivo [38]; however, no studies to our knowledge have assessed Quantum® products in terms of their longevity at low passage.
In the current study, we have assessed the Quantum® system for the isolation and expansion of BM-MSCs directly from bone marrow aspirate and have re-seeded BM-MSCs into the system for a two-phase Quantum® expansion. We have uniquely and comprehensively characterised BM-MSCs and their sub-populations at both expansion phases. In addition, for the first time to our knowledge, we have assessed the Quantum® bioreactor for the up-scale manufacture of UC-MSC using a 'hybrid' process, whereby UC-MSCs have been isolated from tissues onto tissue culture plastic (TCP), as described previously [5,39], and have been re-seeded into the Quantum® for the second expansion phase. We have aimed to comprehens