Cellular engineering and therapy in combination with cord blood allografting in pediatric recipients

Abstract

Cord blood (CB) transplantation is an alternate source of human hematopoietic progenitor cells for allogeneic stem cell transplantation in children and adolescents with both malignant and nonmalignant diseases. Current limitations included delay in hematopoietic reconstitution, increased incidence of primary graft failure and slow cellular immunoreconstitution. These limitations lead to a significant increase in primary graft failure, infectious complications and increased transplant-related mortality. There is a number of experimental approaches currently under investigation including cellular engineering to circumvent these limitations. In this review, we summarize the recent findings of utilizing ex vivo CB expansion with Notch1 ligand Delta 1, mesenchymal progenitor cells, the use of human placenta-derived stem cells and CB-derived natural killer cells. Early and preliminary results suggest some of these experimental cellular strategies may in part ameliorate the incidence of primary graft failure, delays in hematopoietic reconstitution and/or slowness in cellular immune reconstitution following unrelated CB transplantation.

Characterization of the growth modulatory activities of osteoblast conditioned media on cord blood progenitor cells

“…Co-transplantation of a CB unit with ex vivo expanded progenitors has shown to improve engraftment and accelerate neutrophil recovery in CB transplant (Pineault and Abu-Khader 2015;Cairo et al 2016). However, platelets recovery remains a major issue given its extended delays.…”

“…One strategy has been focused on the ex vivo expansion of HSPC prior to transplantation which has now been tested in several clinical trials (Pineault and Abu-Khader 2015;Norkin et al 2013;Delaney et al 2005;Cairo et al 2016;de Lima et al 2012). Indeed, decreased graft failure and accelerated neutrophil recovery have been reported in patients undergoing double CB transplantation with an expanded and unmanipulated units, each unit providing short-and long-term engraftment, respectively (de Lima et al 2012;Delaney et al 2010;Horwitz et al 2014).…”

Efficacy of Human Placental-Derived Stem Cells in Collagen VII Knockout (Recessive Dystrophic Epidermolysis Bullosa) Animal Model

“…Here, HPDSCs are perfusate from full‐term placenta with minimal manipulation. Ongoing clinical studies have demonstrated that adding HPDSCs as an adjuvant with UCBT in patients with malignant and nonmalignant diseases has had no adverse effects and may reduce the incidence of aGVHD .…”

“…Human placental‐derived stem cells (HPDSCs) are a source of stem cells obtained by Celgene Cellular Therapeutics (CCT)'s proprietary process involving perfusion of donated full‐term placentas and depletion of red blood cells, nonviable cells, and tissue debris . Although both HPDSCs and human umbilical cord blood (UCB) originate from placentas, the processing, that is, perfusion of placentas versus gravity collection of blood, has resulted in phenotypic and functional differences between these two cell products.…”

“…Although both HPDSCs and human umbilical cord blood (UCB) originate from placentas, the processing, that is, perfusion of placentas versus gravity collection of blood, has resulted in phenotypic and functional differences between these two cell products. As HPDSCs are largely negative for major histocompatibility complex (MHC) class II molecules, we initiated a pilot study of investigating the safety and efficacy of adding HPDSCs without human leukocyte antigen (HLA) matching (as universal donor cells), in allogeneic UCB transplantation in children and adults with selected malignant and nonmalignant diseases . To date, there have been no adverse events associated with HPDSC infusions in the 35 patients enrolled to date.…”