Chapter 13 Stem Cells and Regenerative Medicine

© 2020 Elsevier Inc. All rights reserved.

Chapter 13

Stem Cells and

Regenerative Medicine

© 2020 Elsevier Inc. All rights reserved. 2

Figure 13–1. The development process from zygote to three germ layers. Through mitosis, the zygote undergoes multiple stages

(morula, blastocyst, and triploblastic gastrula) to form an individual. ESCs are derived from the inner cell mass of blastocysts, which will

develop into embryos. Trophoblasts are derived from the outer cell mass, which will develop into placenta. Three embryonic germ layers,

including ectoderm, mesoderm, and endoderm, are formed in the gastrula period. The formation of these three germ layers lays the

foundation of organs and system development. As the embryo develops, cell totipotency decreases. A small number of mesenchymal

stem cells maintain their multipotency in the differentiated tissues.


Figure 13–2 . Difference in the differentiation potential between ESCs and adult stem cells. ESCs are able to differentiate into nearly all

types of mature cells, while adult stem cells can only produce a limited number of cell types that are specific for their organ of origin.


Figure 13–3. The sources of mesenchymal stem cells (MSCs) and their lineage cells. MSCs are derived from a variety of organs,

including bone marrow, adipose tissue, umbilical cord, placenta, lung, and other organs. As multipotent stromal cells, they can

differentiate into osteoblasts, chondrocytes, hepatocytes, cardiomyocytes, pancreatic cells, adipocytes, etc.


Figure 13–4. The sources of hematopoietic stem cells (HSCs) and their lineage cells. HSCs are mainly derived from bone marrow. They

are also found in umbilical cord blood and, in small numbers, in peripheral blood. HSCs give rise to both the myeloid and the lymphoid

lineages of blood cells, and then differentiate into erythrocyte, thrombocyte, eosinophil, neutrophil, basophil, monocyte, plasma cell, T

lymphocyte, and NK cells.


Figure 13–5. Human iPSCs generation and identification. iPSCs are generated from various somatic cells by the introduction of four

genes: Oct3/4, Sox2, Klf4, c-Myc or Oct3/4, Sox2, NANOG, Lin28, a process called iPSC reprograming. The utmost characteristic of

iPSCs is the same differential totipotency as ESCs, recovering the capacity of differentiating into ectoderm, mesoderm, and endoderm.


Figure 13–6. Stem cell division. Symmetric cell division indicates that one stem cell develops into two differentiated daughter cells or

produces two stem cells identical to the original. The stem cell can also divide into one daughter cell that is identical to the original stem

cell, and another cell that is differentiated through asymmetric cell division.


Figure 13–7. Different potency of stem cells during development. After fertilization, the zygote starts to replicate and divide to form a

morula, with around 30 totipotent cells that can potentially differentiate into all cell types. ESCs within the blastocyst are the descendants

of totipotent cells and can differentiate into nearly all cells. The adult stem cells are multipotent stem cells, being able to differentiate into a

limited number of cell types. As the adult stem cells differentiate, oligopotent cells and unipotent cells are sequentially generated with

further limited differentiation potential, which finally gives rise to the mature cells.


Figure 13–8. Process of tissue repair after injury. The signals released from injury tissue (such as SDF-1 released from ischemic

myocardial tissue) enter circulation and induce mobilization of adult stem cells that reside in niches. The mobilized stem cells then home

to the injury site and differentiate into functional cells or secrete trophic factors to promote tissue repair.


Figure 13–9. Niche and adult stem cells. Signals from the niche determine the status of adult stem cells. In the physiological state, stem

cells reside in the niche and keep self-renewal. Under pathological conditions, stem cells are mobilized and home to the injury site,

facilitating tissue repair. Stem cell therapy mimics the process of stem cell mobilization and homing.


Figure 13–10. Human embryonic stem cell culture and identification. Inner cell mass is isolated from the blastocyst, then the cells are

dissociated into small cell clumps and transferred to fresh feeder layers. ESC lines are established after the splitting of the homogeneous

undifferentiated colonies. ESCs have potential to differentiate into all three lineages (ectoderm, mesoderm, and endoderm).


Figure 13–11. Human adult stem cell culture and identification. Adult stem cells can be obtained from a diversity of tissues. For example,

adipose-derived stem cells are from fat tissue, and bone marrow mesenchymal stem cells are from bone marrow. After being isolated

from the source tissue (single cell mixture for ADSCs, MNCs for BMSCs), cells are seeded in cultural flasks. Following removal of

nonadherent cells by changing culture medium and undergoing culture passaging, ADSCs/BMSCs are enriched and purified.

ADSCs/BMSCs have multidirectional differentiation potential, such as adipogenesis, myogenesis, osteogenesis, chondrogenesis, and

neurogenesis.


Figure 13–12. Strategies of MSC delivery and regenerative medicine. There are three major strategies of MSC delivery in various

settings of regeneration medicine: intravenous injection, local injection, and scaffold-aided stem cell patch.


Figure 13–13. MSC secretome and regenerative medicine. The broad repertoire of MSC secretome makes it a possible strategy for

regenerative medicine, including immunomodulation, CNS regeneration, angiogenesis, cardiac regeneration, musculoskeletal

regeneration, and future enlisted applications.

Chapter 13 Stem Cells and Regenerative Medicine

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