Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment

Horwitz, Mitchell E.; Chao, Nelson J.; Rizzieri, David A.; Long, Gwynn D.; Sullivan, Keith M.; Gasparetto, Cristina; Chute, John P.; Morris, Ashley; McDonald, Charles; Waters‐Pick, Barbara; Stiff, Patrick J.; Wease, Steven; Peled, Amnon; Snyder, David A.; Cohen, Einat Galamidi; Shoham, Hadas; Landau, Efrat; Friend, Etty; Peleg, Ika; Aschengrau, Dorit; Yackoubov, Dima; Kurtzberg, Joanne; Peled, Tony

doi:10.1172/jci74556

Cited by 249 publications

(212 citation statements)

References 23 publications

Supporting

Mentioning

204

Contrasting

Unclassified

Order By: Relevance

“…These include expansion on Notch Ligand, with nicotinamide, and on third-party mesenchymal stem cells. [35][36][37] Additional strategies to increase homing and migration of cord blood cells are also under development using prostaglandin E2, CD 26/dipeptidyl peptidase (DPP-IV) and Fucosylation. [38][39][40] All of these approaches are in early clinical trials and are showing promising results.…”

Section: Ucbt In Pediatricsmentioning

confidence: 99%

Umbilical cord blood donation: public or private?

Ballen

Verter²,

Kurtzberg

2015

Bone Marrow Transplant

View full text Add to dashboard Cite

Umbilical cord blood (UCB) is a graft source for patients with malignant or genetic diseases who can be cured by allogeneic hematopoietic cell transplantation (HCT), but who do not have an appropriately HLA-matched family or volunteer unrelated adult donor. Starting in the 1990s, unrelated UCB banks were established, accepting donations from term deliveries and storing UCB units for public use. An estimated 730 000 UCB units have been donated and stored to date and ∼ 35 000 UCB transplants have been performed worldwide. Over the past 20 years, private and family banks have grown rapidly, storing ∼ 4 million UCB units for a particular patient or family, usually charging an up-front and yearly storage fee; therefore, these banks are able to be financially sustainable without releasing UCB units. Private banks are not obligated to fulfill the same regulatory requirements of the public banks. The public banks have released ∼ 30 times more UCB units for therapy. Some countries have transitioned to an integrated banking model, a hybrid of public and family banking. Today, pregnant women, their families, obstetrical providers and pediatricians are faced with multiple choices about the disposition of their newborn's cord blood. In this commentary, we review the progress of UCB banking technology; we also analyze the current data on pediatric and adult unrelated UCB, including the recent expansion of interest in transplantation for hemoglobinopathies, and discuss emerging studies on the use of autologous UCB for neurologic diseases and regenerative medicine. We will review worldwide approaches to UCB banking, ethical considerations, criteria for public and family banking, integrated banking ideas and future strategies for UCB banking.

show abstract

Section: Ucbt In Pediatricsmentioning

confidence: 99%

Umbilical cord blood donation: public or private?

Ballen

Verter²,

Kurtzberg

2015

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

View full text Add to dashboard Cite

Engraftment outcomes are strongly correlated with the numbers of hematopoietic stem and progenitor cells (HSPC) infused. Expansion of umbilical cord blood (CB) HSPC has gained much interest lately since infusion of expanded HSPC can accelerate engraftment and improve clinical outcomes. Many novel protocols based on different expansion strategies of HSPC and their downstream derivatives are under development. Herein, we describe the production and properties of serum-free medium (SFM) conditioned with mesenchymal stromal cells derivedosteoblasts (OCM) for the expansion of umbilical CB cells and progenitors. After optimization of the conditioning length, we show that OCM increased the production of human CB total nucleated cells and CD34 ? cells by 1.8-fold and 1.5-fold over standard SFM, respectively. Production of immature CD34 ? subpopulations enriched in hematopoietic stem cells was also improved with a shorter conditioning period. Moreover, we show that the growth modulatory activities of OCM on progenitor expansion are regulated by both soluble factors and non-soluble cellular elements. Finally, the growth and differentiation modulatory activities of OCM were fully retained after high dose-ionizing irradiation and highly stable when OCM is stored frozen. In summary, our results suggest that OCM efficiently mimics some of the natural regulatory activities of osteoblasts on HSPC and highlight the marked expansion potentials of SFM conditioned with osteoblasts.

show abstract

“…Additional approaches not covered in this review that are under investigation to accelerate hematopoietic and/or cellular immune reconstitution following UCBT include ex vivo expansion of UCB with nicotinamide and the non-altered T-cell fraction, ex vivo enforced fucosylation with fucosyltransferase IV and guanosine diphosphate fucose, inhibition of dipeptidyl peptidase (DDP-4) by sitagliptin, ex vivo expansion with cytokines and StemRegenin 1 and the use of UCB-derived anti-viral CTLs are just a few of the newer contemporary approaches for ex vivo CB graft engineering being investigated at the present time. [51][52][53][54][55][56] CONFLICT OF INTEREST DAL has financial or ownership interest relating to ex vivo expansion of NK cells in Intrexon Corporation, Ziopharm Oncology and Cyto-Sen Therapeutics. The remaining authors declare no conflict of interest.…”

Section: Resultsmentioning

confidence: 99%

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

Cairo

Tarek

Lee

et al. 2015

Bone Marrow Transplant

View full text Add to dashboard Cite

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.

show abstract

Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment

Cited by 249 publications

References 23 publications

Umbilical cord blood donation: public or private?

Umbilical cord blood donation: public or private?

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

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

Contact Info

Product

Resources

About