The future of human mesenchymal stem cells (hMSCs) as a successful cell therapy relies on bioprocessing strategies to improve the scalability of these cells without compromising their therapeutic ability. The culture-expansion of hMSCs can be enhanced by supplementation with growth factors, particularly fibroblast growth factor 2 (FGF2). The biological activity of FGF2 is controlled through interactions with heparan sulfate (HS) that facilitates ligand-receptor complex formation. We previously reported on an FGF2-interacting HS variant (termed HS2) isolated from embryonic tissue by anionic exchange chromatography that increased the proliferation and potency of hMSCs. Here, we detail the isolation of an FGF2 affinity-purified HS variant (HS8) using a scalable platform technology previously employed to generate HS variants with increased affinity for BMP-2 or VEGF . This process used a peptide sequence derived from the heparin-binding domain of FGF2 as a substrate to affinity-isolate HS8 from a commercially available source of porcine mucosal HS. Our data show that HS8 binds to FGF2 with higher affinity than to FGF1, FGF7, BMP2, PDGF-BB, or VEGF . Also, HS8 protects FGF2 from thermal destabilization and increases FGF signaling and hMSC proliferation through FGF receptor 1. Long-term supplementation of cultures with HS8 increased both hMSC numbers and their colony-forming efficiency without adversely affecting the expression of hMSC-related cell surface antigens. This strategy further exemplifies the utility of affinity-purifying HS variants against particular ligands important to the stem cell microenvironment and advocates for their addition as adjuvants for the culture-expansion of hMSCs destined for cellular therapy. J. Cell. Physiol. 232: 566-575, 2017. © 2016 Wiley Periodicals, Inc.

Background: Current literature suggests the number of HIV clinicians in the United States is diminishing. There are 294,834 primary care providers (PCP) in the United States, and, of these, 3101 provide care to HIV-positive patients. More PCPs to treat and manage HIV patients may be the solution to alleviate the HIV provider shortage. However, PCPs also face challenges, including workforce shortages. We surveyed PCPs to determine perceived barriers, beliefs, and attitudes about their readiness to manage and treat HIV patients. Methods: Following a quantitative, descriptive, cross-sectional survey design, currently practicing clinicians in primary care (physicians, residents, physician assistants, family nurse practitioners) were emailed a link to the study survey. Three hundred forty-seven family medicine clinicians from 47 states met the study inclusion criteria. Results: Most (245/347, 70.6%) of the PCPs agreed that PCPs should take care of HIV patients. PCPs practicing HIV medicine (n = 171) were more likely than those not practicing HIV medicine (n = 176) to agree that PCPs should help with the HIV provider shortage (U = 10,384, p < 0.001) and that PCPs are the best solution to the HIV provider shortage (U = 10,294, p < 0.001). The majority (206, 59.4%) believed PCPs are the best solution for the HIV provider shortage. Of 133 physician assistants (PAs) and family nurse practitioners (NPs), seventy (52.6%) believed they could be ready to manage HIV patients with some training. Conclusion: The HIV provider shortage in the United States is likely to continue. To alleviate the provider shortage, PCPs should be offered additional training, decreased workload, and increased compensation when treating and managing HIV patients. Also, encouraging PAs and family NPs to be involved with HIV medicine may be a solution.

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