Complement Fragment 3a Priming of Umbilical Cord Blood Progenitors: Safety Profile

Brunstein, Claudio G.; McKenna, David H.; DeFor, Todd E.; Sumstad, Darin; Paul, Philip; Weisdorf, Daniel J.; Ratajczak, Mariusz Z.; Laughlin, Mary J.; Wagner, John E.

doi:10.1016/j.bbmt.2013.07.016

Cited by 38 publications

(37 citation statements)

References 30 publications

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“…No adverse effects on survival and no infusional toxicities or activation of inflammatory pathways were observed. Engraftment of the C3a-treated UCB, however, was not impaired or favored relative to non-C3a-treated UCB [167].…”

Section: Complement Componentmentioning

confidence: 72%

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Ex vivo expansion of hematopoietic stem cells

Xie

Zhang

2015

Sci. China Life Sci.

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Ex vivo expansion of hematopoietic stem cells (HSCs) would benefit clinical applications in several aspects, to improve patient survival, utilize cord blood stem cells for adult applications, and selectively propagate stem cell populations after genetic manipulation. In this review we summarize and discuss recent advances in the culture systems of mouse and human HSCs, which include stroma/HSC co-culture, continuous perfusion and fed-batch cultures, and those supplemented with extrinsic ligands, membrane transportable transcription factors, complement components, protein modification enzymes, metabolites, or small molecule chemicals. Some of the expansion systems have been tested in clinical trials. The optimal condition for ex vivo expansion of the primitive and functional human HSCs is still under development. An improved understanding of the mechanisms for HSC cell fate determination and the HSC culture characteristics will guide development of new strategies to overcome difficulties. In the future, development of a combination treatment regimen with agents that enhance self-renewal, block differentiation, and improve homing will be critical. Methods to enhance yields and lower cost during collection and processing should be employed. The employment of an efficient system for ex vivo expansion of HSCs will facilitate the further development of novel strategies for cell and gene therapies including genome editing. ex vivo expansion, hematopoietic stem cells, niche, signal transduction, cord blood, transplantation, SCID-repopulating cell, genome editing, CRISPR/Cas9 Citation:Xie JJ, Zhang CC. Ex vivo expansion of hematopoietic stem cells.

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Section: Complement Componentmentioning

confidence: 72%

“…A simple priming of one UCB unit with C3a for 15 min followed by double UCB transplantation was performed in a phase I study [167]. No adverse effects on survival and no infusional toxicities or activation of inflammatory pathways were observed.…”

Section: Complement Componentmentioning

confidence: 99%

Ex vivo expansion of hematopoietic stem cells

Xie

Zhang

2015

Sci. China Life Sci.

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“…Double cord blood transplantation has been extensively investigated but, to date, a survival advantage has not been shown over single UCB units or unrelated donor grafts 7,28-37 and additional efforts are being investigated in clinical trials. 4,38,39 As these attempts are explored and potentially practice-changing data emerges, improvements and expertise in our current transplant procedures are of great importance.…”

Section: Discussionmentioning

confidence: 99%

A prospective investigation of cell dose in single-unit umbilical cord blood transplantation for adults with high-risk hematologic malignancies

Sobol

Kliethermes

et al. 2015

Bone Marrow Transplant

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Umbilical cord blood (UCB) as an allogeneic transplant source is generally limited to units with pre-cryopreservation total nucleated cell (TNC) doses ⩾ 2.5 × 10 7 NC/kg. We prospectively investigated single UCB transplantation, with cord units as low as 1 × 10 7 NC/kg, all processed with post-thaw albumin-dextran dilution. We transplanted 104 adult patients with 84% having relapsed/ refractory disease. The median TNC dose was 2.1 × 10 7 NC/kg (range: 1.0-4.4 × 10 7 ) and median CD34+ cell dose was 1.0 × 10 5 /kg (range: 0.0-3.7 × 10 5 /kg). Post-manipulation cell recovery and viability were 96% and 99%, respectively. Median times to neutrophil and platelet engraftment were 16 and 43 days, respectively. Univariate factors predicting neutrophil engraftment included TNC (P = 0.03) and CD34+ cell dose (P = 0.01). CD34+ dose predicted platelet engraftment (P o0.001). In multivariate analysis, CD34+ dose remained significant for neutrophil and platelet engraftment (P o0.0001 and P o 0.0001, respectively). The 100-day and 1-year overall survival were 70% and 46%, respectively (95% confidence interval: 36%-56% at 1 year). The subset transplanted with 1-1.5 × 10 7 NC/kg had similar 100-day and 1-year survivals of 73% and 45%, respectively. Single-unit UCB transplantation using small units, processed as described, leads to favorable engraftment and acceptable outcomes in poor prognosis patients. CD34+ cell dose (⩾1.5 × 10 5 /kg) helps predict faster engraftment and can aid in graft selection.

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“…This complement pathway protein is produced by bone marrow MSCs and interacts with the C3aR on UCB HSPCs to enhance CXCL12-mediated migration [100,101]. A Phase I clinical trial involving C3a priming of a one of the two UCB units in the nonmyeloablative conditioning double cord blood seting [101] did not, however, demonstrate preferable neutrophil recovery in the manipulated UCB unit in most cases, although the CD3 content of the graft correlated with engraftment. Lund et al [102] have reviewed this trial recently and concluded that the study has added value for designing further clinical trials using manipulated and unmanipulated double UCB units.…”

Section: IImentioning

confidence: 99%

Umbilical Cord Blood Hematopoietic Stem and Progenitor Cell Expansion for Therapeutic Use

Watt¹,

Hua²

2017

Umbilical Cord Blood Banking for Clinical Application and Regenerative Medicine

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Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for severe hematological malignancies and other severe disorders of the blood, immune system, and bone marrow. It is the most successful regenerative therapy to date, with 2013 marking the one millionth HSCT and the 25th anniversary of the irst umbilical cord blood (UCB) HSCT. UCB has most often been used for allogeneic HSCT when a matched bone marrow or peripheral blood donor is unavailable. Recently, novel genome editing technologies to correct inherited gene disorders or to modulate biomarkers/ receptors on HSC and the potential use of HSCT for a variety of other nonmalignant conditions have led to a surge of interest in autologous HSCT, with the HSC source depending on the condition to be treated. UCB HSCs may be used to generate red blood cells, granulocytes, or platelets ex vivo for transfusion into diicult-to-transfuse patients. Alternatively, UCB may be reprogrammed to induced pluripotent stem cells or used to generate cell lines, which can then be diferentiated into diferent cell lineages for transfusion or used as diagnostic reagents. Disadvantages of UCB are its restricted cell numbers and delayed hematological engraftment. Here, UCB HSC expansion/ manipulation ex vivo and clinical applications are addressed.

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Complement Fragment 3a Priming of Umbilical Cord Blood Progenitors: Safety Profile

Cited by 38 publications

References 30 publications

Ex vivo expansion of hematopoietic stem cells

Ex vivo expansion of hematopoietic stem cells

A prospective investigation of cell dose in single-unit umbilical cord blood transplantation for adults with high-risk hematologic malignancies

Umbilical Cord Blood Hematopoietic Stem and Progenitor Cell Expansion for Therapeutic Use

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