Documentos de Académico
Documentos de Profesional
Documentos de Cultura
REVIEW
Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union
Medical College, Beijing 100005, China
Abstract Regenerative medicine is an emerging interdisciplinary eld of research that uses several technological
approaches including stem cells to repair tissues. Mesenchymal stem cells (MSCs), a type of adult stem cell, have
generated a great amount of interest over the past decade in this eld. Numerous studies have explored the role of
MSCs in tissue repair and modulation of allogeneic immune responses. The mechanisms through which MSCs
exert their therapeutic potential rely on some key properties of the cells as follows: the capacity to differentiate into
osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes, endothelial, and neuronal cells; the ability to
secrete multiple bioactive molecules capable of stimulating the recovery of injured cells and inhibiting
inammation; the lack of immunogenicity; and the ability to perform immunomodulatory functions. In the
present review, we focus on these three aspects upon which the therapeutic effects of MSCs are mainly based.
Furthermore, some pathological conditions under which the application of MSCs should be done with caution are
also mentioned.
Keywords
Introduction
Regenerative medicine is an emerging interdisciplinary eld
of research and clinical applications focused on the repair,
replacement, or regeneration of cells, tissues, or organs to
restore impaired function resulting from multiple causes,
including congenital defects, disease, and trauma. Regenerative medicine uses a combination of several technological
approaches that transcend beyond traditional transplantation
and replacement therapies. These approaches include, but are
not limited to, the use of stem cells [1]. Many different types
of stem cells can be used for regenerative medicine, including
the following: (1) Embryonic stem cells derived from the
inner cell mass of the blastocyst, and can produce the entire
repertoire of cells in the body. However, they form teratoma
when transplanted directly, and they are ethically controversial. (2) Adult stem cells, which are already somewhat
specialized and have limited differentiation potential. They
can be isolated from various tissues and are currently the most
commonly used seed cells in regenerative medicine. One
example is hematopoietic stem cells (HSCs), which sustain
blood formation throughout our entire lives and are restricted
373
Table 1
tubular epithelium at an early stage of injury. The differentiated donor cells replaced the vacant space left by the
dead cells, thereby contributing to the maintenance of
structural integrity and proceeding to a subsequent tissuerepair process [17]. In Wistar rat models of diabetic
retinopathy, transplanted MSCs differentiated into photoreceptor and glial-like cells in the retina, which improved the
integrity of the blood-retinal barrier in diabetic rats [18]. In
mdx mice, AD-MSCs homed on the injured muscle tissues
and differentiated into myotubes and endothelial cells, as well
as muscle satellite cells [19]. Other examples of the use of
MSC to treat diseases through differentiation are shown in
Table 2.
Tissue
Term placental membranes
Reference
[10]
[11]
Amniotic uid
All embryonic germ layers, including neuronal lineage cells secreting the neurotransmitter L-glutamate or
expressing G-protein-gated inwardly rectifying potassium channels, hepatic lineage cells producing urea,
and osteogenic lineage cells forming tissue-engineered bone
[12]
Adipocytes and osteoblast-like cells (mesoderm), glucagon and insulin expressing pancreatic-like cells
(endoderm), as well as cells expressing the neuronal markers neuron-specic enolase, glutamic acid
decarboxylase-67 (GAD), or class III beta-tubulin, and the astrocyte marker glial brillary acidic protein
(ectoderm)
[13]
All three germ layersendoderm (liver, pancreas), mesoderm (cardiomyocyte), and ectoderm (neural
cells) in vitro
[14]
In vitroosteoblasts, chondroblasts, adipocytes, and hematopoietic and neural cells including astrocytes
and neurons that express neurolament, sodium channel protein, and various neurotransmitter phenotypes.
In vivomesodermal and endodermal lineages demonstrated in animal models
[15]
[16]
374
Table 2
Disease model
Lung injurythe thoraxes of C57BL/6 mice
were exposed to 1 400 cGy
Detailed information
Reference
MSCs injected immediately after injury were shown to differentiate into functional lung cells,
[20]
such as epithelial and endothelial cells
MSCs differentiated in response to local cues into endothelial cells and contributed to
neoangiogenesis
[21]
MSCs engrafted into host liver, had epithelium-like morphology, and expressed albumin,
although at a low frequency
[22]
Fluorescence-labeled Flk + MSC of BALB/c mice (H-2Kd, white) were transplanted into lethally
irradiated C57BL/6 mice (H-2Kb, black); donor cells could migrate and take residency at the
skin. The recipient mice grew white hairs after approximately 40 days. Immunochemistry
staining and RT-PCR demonstrated that skin tissue within the white hair regions was largely
composed of donor-derived H-2Kd cells, including stem cells and committed cells. Furthermore,
most skin cells cultured from white hair skin originated from the donor. Thus, these ndings
provide direct evidence that bone marrow-derived cells can give rise to functional skin cells and
regenerate skin tissue
[23]
Table 3
Bioactive molecules
Prostaglandin E2
Functions
Anti-proliferative mediators
Interleukin-10
Anti-inammatory
[27]
Anti-inammatory
[28]
LL-37
[31,32]
[33,34]
Reference
[24]
[25,26]
[29,30]
mismatched
allogeneic
transplantation
following
nonmyeloablative conditioning [45]. We explored the
efcacy and safety for treating chronic graft-versus-host
disease (cGVHD), particularly sclerotic skin manifestations
of cGVHD (ScGVHD) by MSC transplantation. Patients with
ScGVHD had improved symptoms after receiving MSC
expanded ex vivo from unrelated donors by intra-BM
injection [46]. Based on studies in our laboratory, we drew
a schematic picture of the immunomodulatory effects of
MSCs both in vitro and in vivo (Fig. 1).
375
376
Acknowledgements
This work was supported by grants from the 863 Projects of
Ministry of Science and Technology of P. R. China (No.
2011AA020100), the National Natural Science Foundation of
China (Grant No. 30830052), the National Key Scientic Program
of China (No. 2011CB964901), and the Program for Changjiang
Scholars and Innovative Research Team in University (PCSIRT)
(No. IRT0909).
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