From the Desk of Todd Schuesler, Director of Laboratory Operations
Stem Cell
Insider
Issue 8
THE INSIDER
IN BRIEF
Ex vivo expansion has the
potential to greatly increase
the use of cord blood stem
cells as a standard of disease
treatment.
A number of ex vivo expansion
studies are in the second and
third phase, suggesting that
protocols are proving safe
and feasible.
Data show that neutrophil
engraftment was significantly
accelerated in the more
recent studies and, in some
cases, platelet recovery was
also statistically improved.
Enhancing Cord Blood Banking through Advancements
in Expansion Technologies
An exciting advancement in cord blood banking is the progress being made to dramatically
increase the number of stem cells in a cord blood unit.
EXPANDING CELL COUNTS Recent studies have also been using novel molecules
Ex vivo expansion has the potential to greatly such as HSC835 (Novartis) and MGTA456
(Magenta) or mesenchymal stromal cell (MSC) co-
increase the use of cord blood stem cells as a
culturing, which is a promising strategy to mimic the
standard treatment. A growing number of studies
physiological microenvironment within the marrow.
are looking at various methods of expanding cord
blood stem cells, and a number of these studies are
in the second and third phases, suggesting that ex FINDINGS
vivo expansion protocols are proving safe, effective Compared with historical controls, neutrophil
and feasible. engraftment was significantly accelerated in the
more recent studies using small molecule or MSC
These expansion technologies are so promising
that they have attracted small and big pharma with co-culturing, and in some cases, platelet recovery
was also statistically improved. Results of larger
investments and products from Novartis, Mesoblast,
randomized controlled trials are needed to
Gamida Cell, Magenta and Excellthera. A systematic
understand the impact on patient outcomes and
review of current studies regarding cord blood–
health-care costs.
expanded products shows that time to neutrophil
engraftment—a benchmark used to denote patient
recovery—can be reduced.
EXPANSION TYPES
Most of the ex vivo expansion studies thus far have
involved the co-infusion of an expanded unit, or a
part thereof, and a second unmanipulated unit, or
fraction thereof.1
The evolution of expansion studies reflects the READY FOR ACTION— Stem cells extracted from cord
progression being made in the stem cell industry’s blood and not treated with UM171 (left) appeared less
understanding of the topic. Early studies used robust than similar cells treated with UM171 (right).2
cytokine combinations for expansion, but since
2008, the introduction of additional small A similar trend was observed for hematopoietic stem
molecules or feeder cell layers has been used cell (HSC) expansion with novel small molecules
to augment the effect of defined cytokine and MSC co-culturing leading to more significant
combinations. Specifically, the use of the expansion and a higher number of HSCs infused into
following have been shown to either inhibit patients.
HSC differentiation or promote HSC self-
renewal or accomplish both: A number of individual studies observed that
transplantation of expanded cord blood reduced the
median days to neutrophil engraftment compared
• Copper chelator with historical double-cord transplant controls, with
some studies reporting statistical significance in the
• Tetraethylenepentamine (TEPA)
time to neutrophil recovery. All studies that reported
• Notch ligand a statistically significant improvement in median
• UM171 neutrophil recovery rates versus controls used
cytokines in combination with novel small molecules
• StemReginin-1 or with MSC co-culturing in the expansion protocol.
• Nicotinamide (Nicord)
SEE REVERSE SIDE FOR CONCLUSION & LIST OF EXPANSION TRIALS; VISIT CLINICALTRIALS.GOV FOR MORE INFO.
 Parents may be more receptive to future clinical trials knowing
they will not have to use the entirety of the stem cell collection.

CLINICAL TRIALS INVOLVING EX VIVO EXPANSION OF CORD BLOOD STEM CELLS

STATUS AS OF
STUDY NAME STUDY NUMBER FACILITY AGENT
11/2017

Study of UM171-Expanded Cord Blood in Patients Who Need an Allogeneic Maisonneuve–Rosemont

NCT02668315 UM171 Recruiting
Hematopoietic Stem Cell Transplant But Lack a Suitable Donor (Phase I–II) Hospital

Study of Single or Double Myeloablative Cord Blood With or Without Infusion of

Fred Hutchinson Cancer
Off-The-Shelf Ex Vivo Expanded Cord Blood Cells in Hematologic Malignancies NCT01690520 N/A Recruiting
Research Center
(Phase II)

Study of Umbilical Cord Blood Cells Expanded With MPCs for Transplantation in Mesenchymal
NCT01854567 Multi-National Active
Patients With Hematologic Malignancies (Phase III) stem cells

Allogeneic Stem Cell Transplantation of NiCord®, Umbilical Cord Blood-derived

NCT01816230 Gamida Cell ltd NiCord Active
Ex Vivo Expanded Cells, in Hematological Malignancies (Phase I–II)

CordIn(TM), Umbilical Cord Blood-Derived Cells to Expedite Engraftment and

NCT03173937 Gamida Cell ltd CordIn Recruiting
Improve Transplant Outcome (Phase I–II)

Allogeneic Stem Cell Transplantation of CordIn™, Umbilical Cord Blood-Derived

NCT02504619 Gamida Cell ltd CordIn Recruiting
and -Expanded Cells, in Hemoglobinopathies (Phase I–II)

Allogeneic Stem Cell Transplantation of NiCord®, Umbilical Cord Blood-Derived,

Ex Vivo–Expanded Cells, in Combination With a Second, Unmanipulated Cord NCT01590628 Gamida Cell ltd NiCord Recruiting
Blood Unit in Hemoglobinopathies (Phase I–II)

Study to Evaluate Infusing HSC835 (LFU835-expanded Cells) in Hematological

NCT01474681 Novartis HSC835 Recruiting
Malignancies (Phase I–II)

Trial of Transplantation of NiCord®, Ex Vivo–Expanded, UCB-derived, Cells, and

NCT02730299 Gamida Cell ltd NiCord Recruiting
Unmanipulated UCB for Hematological Malignancies (Phase III)

Donor Cord Blood Cell Infusion Following Chemotherapy in Younger Patients With Fred Hutchinson Cancer
NCT01701323 Notch Recruiting
Relapsed or Refractory Acute Myeloid Leukemia (Phase I) Research Center

Randomized Double Cord Blood Transplant Study (Phase II) NCT00067002 Gamida Cell ltd NiCord Recruiting

To get more details on the above clinical trials or other clinical trials related to expansion of cord blood stem cells,
please visit clinicaltrials.gov.

CONCLUSION
It appears increasingly likely that expansion practices will be firmly established by the FDA and that researchers and doctors will have
the ability to use just a portion of a collection to grow more stem cells. This would allow for the more widespread use of a single cord
blood unit in adults or provide the opportunity for multiple treatments to be obtained from a single unit. Parents will then be more
receptive to future clinical trials knowing that they will not have to use the entirety of their baby’s cord blood collection. 3 This, in turn,
can greatly expand the use of cord blood stem cells as a standard treatment.

SOURCES:
1. Kiernan J, Damien P, Monaghan M, et al. : Clinical Studies of Ex Vivo Expansion to Accelerate Engraftment After Umbilical Cord Blood
Transplantation: A Systematic Review. Transfus Med Rev. 2017;31(3):173–82. 10.1016/j.tmrv.2016.12.004
2. Photo taken from http://www.sciencedaily.com/releases/2014/09/140918141155.htm 1. Wierenga, P.K., Brenner, M.K., and Konings, A.W.T.
(1998) Bone Marrow Transplantation 21:73–78.
3. Driscoll, Kimberly A., Suzanne Bennett Johnson, Desmond A. Schatz, and Michael J. Haller. “Use of a Precious Resource: Parental Decision
Making about Using Autologous Umbilical Cord Blood in Studies Involving Young Children with Type 1 Diabetes.” Contemporary Clinical
Trials 32.4 (2011): 524–29.

ABOUT CRYO-CELL INTERNATIONAL

Cryo-Cell International Inc. was founded in 1989. Its mission is to provide clients with the premier stem cell
cryopreservation service and to support research and development initiatives for regenerative medicine. In 1992,
Cryo-Cell International became the first company in the world to separate and store stem cells from umbilical
cord blood. Cryo-Cell’s leadership is recognized worldwide as evidenced by the licensing of our technology and
service offering to three of the world’s top seven private cord blood banks.
700 Brooker Creek Blvd. • Suite 1800 Over 500,000 parents from 87 countries trust Cryo-Cell to store their stem cells.* Through research partnerships
• Oldsmar, FL 34677 • with Saneron-CCEL Therapeutics, Stanford University and others, the company remains on
800.786.7235 • Cryo-Cell.com the forefront of regenerative medicine.
*Includes specimens from Cryo-Cell International’s affiliates in Mexico and India. Regarding umbilical cord tissue, all private blood banks’ activities for New York State residents are limited to collection, processing,
and long-term storage of umbilical cord tissue stem cells. The possession of a New York State license for such collection, processing and long-term storage does not indicate approval or endorsement of possible future
uses or future suitability of these cells. ©2017 Cryo-Cell International. All rights reserved. POT0024_1117B