Atrophic Kidney-Like Lesion-Case Report and Review of the Literature.

Atrophic kidney-like lesion (AKLL) is a rare kidney lesion, which was recently suggested by the Genitourinary Pathology Society as a provisional entity. As of now, 16 examples of AKLL have been described in the literature. Here we report a new tumor which shows similar clinicopathologic characteristics with those previously reported in AKLL. Immunohistochemical (IHC) studies in the current lesion identified a biphasic staining pattern consisting of a mixture of WT1+/KRT7-/PAX8- large dilated cysts and WT-/KRT7+/PAX8+ small atrophic cysts. Histomorphologic features of AKLL overlap with several neoplastic and non-neoplastic entities which can lead to mischaracterization. Awareness of the differentiating features is likely important when evaluating these lesions.

Final Outcomes from a Phase 2 Trial of Posoleucel in Allogeneic Hematopoietic Cell Transplant Recipients.

Allogeneic hematopoietic cell transplantation (allo-HCT) recipients are susceptible to viral infections. We conducted a phase 2 trial evaluating the safety and rate of clinically significant infections (CSIs; viremia requiring treatment or end-organ disease) following infusion of posoleucel, a partially HLA-matched, allogeneic, off-the-shelf, multivirus-specific T cell investigational product for preventing CSIs with adenovirus, BK virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus-6, or JC virus. This open-label trial enrolled high-risk allo-HCT recipients based on receiving grafts from umbilical cord blood, haploidentical, mismatched, or matched unrelated donors; post-HCT lymphocytes <180/mm3; or use of T cell depletion. Posoleucel dosing was initiated within 15-49 days of allo-HCT and subsequently every 14 days for up to seven doses. The primary endpoint was the number of CSIs due to the six target viruses by week 14. Of the 26 patients enrolled just three (12%) had a CSI by week 14, each with a single target virus. In vivo expansion of functional virus-specific T cells detected via interferon-γ ELISpot assay was associated with viral control. Persistence of posoleucel-derived T cell clones for up to 14 weeks after the last infusion was confirmed by T cell receptor deep-sequencing. Five patients (19%) had acute GVHD grade II-IV. No patient experienced cytokine release syndrome. All six deaths were due to relapse or disease progression. High-risk allo-HCT patients who received posoleucel had low rates of CSIs from six targeted viruses. Repeat posoleucel dosing was generally safe and well tolerated and associated with functional immune reconstitution. www.clinicaltrials.gov NCT04693637.

Células-tronco mesenquimais para reparo clínico / Allogeneic mesenchymal stem cells for cardiac repair

As células tronco mesenquimais (CTMs) são uma população adulta de células que compartilham algumas características fenotípicas com as células-tronco embrionárias, mas carecem da preocupação ética ou da segurança associadas a tais células indiferenciadas. As CTMs estão localizadas, principalemnte na médula óssea e, em menor grau, em outros tecidos. Elas podem ser positivamente selecionadas, expandidas em cultura ex vivo e se diferenciar para a linhagem de osteócitos, condrócitos e adipócitos do tecido mesenquimal. As chamadas células mesenquimais progenitoras (CMPs), precusoras de CTMs, podem ser isoladas da medula óssea, resultando em produto homogêneo, contendo uma população marcadamente mais pura de CTMs, ou seja, sem o elevado número de células contaminantes...

Mesenchymal stem cells (MSCs) are an adult stem cell population that share some phenotypic characteristics with embryonic stem cells but lack the ethical or safety concerns associated with such undifferentiated cells. MSCs are located primarily in the bone marrow and to a lesser extent other tissues and can be positively selected, ex vivo culture expanded and are able to differentiate into the mesenchymal tissue lineage of osteocytes, chondrocytes and adipocytes. A precursor of MSCs termed mesenchymal progenitor cells (MPCs) can be further isolated from bone marrow resulting in a homogenous product containing a significantly purer population of MSCs without the high number of contaminating cells inherent toMSC isolation techniques. Additionally, MSCs lack certain co-stimulatory receptors such as HLA class II and locally secrete factors downregulating T cell responses allowing for allogeneic usage as an off-the-shelf product. MSCs increase neovascularization and cardiomyocyte regeneration in a number of animal models resulting in improvement in cardiac functional outcome and limitation of the progression to heart failure. The mechanism(s) of improvement remains a matter of debate. Alternatives include direct differentiation of the MSCs vs. paracrine secretion of factors that indirectly effect endogenous tissue and local progenitor cells. While the exact mechanism of cardiac improvement continues to be explored, it is clear that allogeneic MSCs offer a reproducible, inexpensive, regulatory-friendly cellular therapy treatment for cardiovascular disease that will need to be investigated in larger safety and efficacy clinical trials.