Mini Review
The Functions and Characteristics of Hematopoietic Stem/Progenitor Cells Derived From Umbilical Cord Blood and its Clinical Application in Transplantation
Song K1*, Lu Y1, Tian J1, Jiao Z1, Wang Y2 and Liu T1
1State Key Laboratory of Fine Chemicals, Dalian University of Technology, China
2Burns Research Group, ANZAC Research Institute, University of Sydney, Australia
*Corresponding author: Kedong Song, Dalian University of Technology, Dalian R&D Center for Stem Cell and Tissue Engineering, No.2 Linggong Road, Dalian 116024, China
Published: 08 Sep, 2016
Cite this article as: Song K, Lu Y, Tian J, Jiao Z1
Wang Y, Liu T. The Functions and
Characteristics of Hematopoietic Stem/
Progenitor Cells Derived From Umbilical
Cord Blood and its Clinical Application
in Transplantation. Clin Oncol. 2016; 1:
1082.
Abstract
Umbilical cord blood (UCB) contains abundant portable cord blood hematopoietic stem/progenitor
cells (HSPCs) that can be used as a substitute to human marrow in the reconstruction of the
hematopoietic and immune system. Firstly, this article expounds the functions and characteristics
of hematopoietic stem cells and hematopoietic progenitor cells and the differences between UCB
HSPCs and marrow HSPCs in function, then, introduces the principle of hematopoietic stem cell
transplantation and the advantages and weaknesses of UCB HSPCs transplantation. The application
of UCB transplantation in the clinic are also discussed.
Keywords: UCB HSPCs; Function and characteristic; Clinical transplantation
Introduction
UCB is blood that residues in the umbilical cord and placenta, and is usually discarded following child birth. In the late 1980s, physicians discovered that cord blood contained HSPCs, however it’s clinical potential and significance was not recognized. It was only in 1989 that the Broxmeyer team [1]. Found that cord blood contained abundant portable HSPCs which could be used as a substitute to marrow for hematopoietic reconstruction by semi-quantitative experiments. Following this study, Gluckman et al. [2] successfully transplanted HLA UCB in children who suffered from Fanconi anemia. It proved that the UCB can be successfully applied to the clinic and can be used replace the marrow as a source of HSPCs. Since then, cord blood collection and its clinical application has increased. A large number of studies have confirmed that UCB contains abundant HSPCs and can be used for transplantation to rebuild hematopoies is and immune system function. To date this method can effectively treat more than 80 types of diseases, in particular diseases associated with the immune system and blood system.
Functions and Characteristics of UCB Hematopoietic Stem/Progenitor Cells
HSPCs consist of partial hematopoietic stem cells and a majority of hematopoietic progenitor
cells. These two cells possess different characteristics that give rise to their distinct functions.
Hematopoietic stem cells are a small group of the most primitive hematopoietic cells which possess
multi-directional differentiation potential and high self-renewal ability. Hematopoietic stem cells
can differentiate into 8 different types of cells in the hematopoietic system, including erythrocyte,
neutrophil/granulocyte, monocyte/macrophage, eosinophile, basophilic granulocyte/mastocyte,
megacaryocyte/soterocyte, B lymphcyte and lymphocyte T [2]. Hematopoietic stem cells always
exist in the body, to maintain the quantitative and qualitative balance of all department cells and to
ensure permanent hematopoietic reconstruction after transplantation.
In contrast, hematopoietic progenitor cells are a large number of hematopoietic cells that possess
a reduced ability for self-renewal, but can undergo high rates of proliferation and differentiation.
In the early stage, hematopoietic progenitor cells are capable of differentiating into myeloid and
lymphoid progenitor cells that are able to undergo further differentiation within their own sublines
to form more mature cells. These two characteristics mean hematopoietic progenitor cells are
able to maintain hematopoies is and immune reconstruction function only for a short term after
transplantation.
The differences in the functions of UCB HSPCs and marrow
HSPCs can be attributed to the following factors [3,4]. (1) UCB
HSPCs have lower maturity, longer telomeres and high telomerase
activity, which confers higher proliferation potential in UCB HSPCs
[2]. Compared to adult cells, UCB HSPCs have high self-renewal
ability [4]. UCB HSPCs are less sensitive to inhibitory factors (such
as tumor necrosis factor-a, interferon-a, etc.), but are more sensitive
to stimulatory hematopoietic growth factors, so HSPCs can amplify
more efficiently under the action of cytokines [4]. In the resting stage,
UCB HSPCs can quickly exit the G0/G1 period (the dormant period).
Any of the following mechanisms can be attributed to UCB HSPCs
efficient amplification potential [5]. UCB plasma may promote
cord blood cells to exit the dormant period, or high concentrations
of cytokines (such as IL-6, G-CSF, etc.) in plasma may play a
stimulating effect [6]. UCB HSPCs can release hematopoietic factors
in an autocrine manner to promote the formation of colonies [7].
The content of lymphocyte T in cord blood is relatively small, which
reduces the immunogenicity of UCB HSPCs and widens the HLA
mismatch tolerance range.
Table 1
Figure 1
Clinical Application of Umbilical Cord Blood Transplantation
Umbilical cord blood hematopoietic stem / progenitor cell
transplantation
The basic principles of hematopoietic stem cell transplantation
involve patients receiving high-doses of radiotherapy or
chemotherapy, in combination with the use of immune suppression
drugs to clear tumor cells in the host body. Autologous or allogeneic
hematopoietic stem cells are then delivered to restore normal
hematopoietic and immune function. Although commonly known
as "hematopoietic stem cell transplantation", a more accurate term
for this procedure would be hematopoietic stem / progenitor cell
transplantation. From all CD34+ hematopoietic stem cells isolated
from three different sources (bone marrow, umbilical cord blood
and peripheral blood), more than 90% are hematopoietic progenitor
cells, while hematopoietic stem cells only account for a small part.
Theoretically, the most ideal graft should include: hematopoietic stem
cells, a large number of hematopoietic progenitor cells, stromal cells
and their products.
In the process of HSPCs transplantation, two major challenges are
often encountered [1,5]. Whether the donor's white blood cell antigen
(HLA) is consistent with the receptor [2]. The incidence of graft versus
host disease after transplantation. The feasibility of using umbilical
cord blood for HSPCs grafts have been questioned by clinicians.
HSPCs transplantation can be divided into autologous and allogeneic
HSPCs transplantation. Depending on the relationship between the
donor and the patient, allogeneic HSPCs transplantation can be
divided into blood related and unrelated donors. Although there are
some advantages to autologous and blood related transplantation,
difficulty finding HLA matched donors, the complexity the long cycle
of the transplant process, represent some disadvantages and limit the
use of the two methods in clinical practice at present.
Due to umbilical cord blood HSPCs unique biological
characteristics, convenient sources and wide range of transplant
adaptability, umbilical cord blood transplantation has been developed
most recently over the past 30 years. Compared with traditional bone
marrow transplantation, the characteristics of umbilical cord blood
transplantation are shown in (Table 1).
Clinical application of umbilical cord blood transplantation
Because of the unique composition and biological features of
umbilical cord blood HSPCs, and advantages of cord blood HSPCs
transplantation, umbilical cord blood transplantation has been
widely used in clinical practice. It’s field of application has been
extended to non-hematologic diseases and can also be applied for
cell regeneration and immune regulation [7]. (Figure1) is current
clinical trial of umbilical cord blood transplantation in the treatment
of umbilical blood and non-blood type of the disease. Since the
umbilical cord blood is rich in vascular progenitor cells, a 27-yearold
female patient who has the Behcet multi-system disease was
effectively treated by vascular graft surgery [8]. Lv et al. [9], explores
the safety and efficiency in treating autistic children by combining
umbilical cord blood mononuclear cells with umbilical cord bloodderived
mesenchymal stem cells. The results showed that the effect
of combined transplantation of the two types of cells is better than
umbilical cord blood-derived mononuclear cell transplantation
alone. Lima et al. [10], studied the effect of two umbilical cord blood
transplantations in the treatment of adult patients with hematological
malignancies, in which one umbilical cord blood contained the
in vitro amplified autologous MSCs. The result showed that the
combined treatment with in vitro amplified autologous MSCs can
enhance the safety and efficiency of transplantation.
The disadvantages of umbilical cord blood stem/progenitor cell
transplantation can be attributed to two factors [11,12], (1) The
absolute amount of HSPCs and overall number of nucleated cells
is is too low; this poses a major problem when more nucleated cells
are required when there is a higher level of HLA mismatch. (2) After
umbilical cord blood transplantation, patients are prone to relapse
because of graft failure, hematopoietic delay and low incidence of
GVHD. These disadvantages can be addressed by the following
methods (1) In vitro amplification can directly amplify umbilical
cord and also can isolate mononuclear cells or CD34+ cells which
can increase the absolute amount of HSPCs; (2) A one-time two
reinfusion of umbilical cord blood or a umbilical cord blood and cell
amplification; (3) Utilize modified treatment to umbilical cord blood
to facilitate the homing ability of HSPCs in transplant to marrow;
(4) Increase virus-specific T cells in umbilical cord blood, transducer
tumor-specific diseases chimeric antigen receptor, amplify NK cells
and regulatory T cells in order to prevent the incidence of relapse
and GVHD; (5) Bone marrow cavity injection which can improve the
homing efficiency of transplanted cells [13].
Acknowledgement
This work was supported by the Fok Ying Tung Education Foundation (132027), National Natural Science Foundation of China (31370991/31170945), the State Key Laboratory of Fine Chemicals (KF1111), the Joint Open Foundation of Natural Science Foundation of Liaoning and Shenyang National Laboratory for Materials Science (2015021017) and the Fundamental Research Funds for the Central Universities (DUT14YQ106/DUT15QY47/16ZD210) and SRF for ROCS, SEM.
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