**2.1 Non-embryotic autologous adult stem cells**

*Regenerative Medicine*

marrow.

surgeries.

**2. What are stem cells?**

or brain cell is functionally specific.

different lineages under appropriate conditions.

as they are found almost in every type of tissue. Regenerative medicine treatment options using autologous stem cells can be safely executed by well-trained physicians at point of care (POC). This review is not meant to be exhaustive, but our aims are to shed light on the bone marrow progenitor and stem cell mechanisms and highlight present and future applications of autologous bone marrow-derived stem

In this chapter a definition is provided on embryotic and non-embryotic stem cells, followed by an intensive review of non-embryotic autologous adult stem cells. The use of allogeneic MSCs, the fabrication of engineered constructs by seeding of natural or synthetic scaffolds with cells, released from autologous tissues will not be presented in this chapter, as only relatively few of these cell-based approaches have entered the clinical arena. In particular, we deliberate on the biology and clinical application of mesenchymal stem cells originating from freshly harvested bone marrow. We portray on the techniques of a marrow harvesting procedure using ultrasound and fluoroscopic techniques. Explicit scientific information is provided on the bone marrow aspirate cellular content, their specific biological functions and intercellular interactions, as these, among others, contribute to tissue regeneration following clinical regenerative medicine applications. Furthermore, we underline the differences between bone marrow aspirate and, centrifugated, bone marrow aspirate concentrate injectates, both prepared at point of care from freshly aspirated

Finally, a condensed literature review addressing a variety of clinical orthobiological indications, spinal disorders, chronic wounds, and critical limb ischemia is provided. Regenerative medicine technologies, using marrow-derived mesenchymal stem cell-based therapies, as part of the regenerative medicine treatment armamentarium, offer solutions to a number of undeniable clinical conditions that have not been able to adequately result in a solution through the use of medicines or

Becker, McCulloch, and Till first conducted experiments that lead to the discovery of stem cells in 1963. After injecting bone marrow cells into irradiated mice, nodules developed in proportion to the number of bone marrow cells injected, and they concluded that each nodule arose from a single marrow cell. At a later stage, they produced evidence that these cells were capable of endless self-renewal, which is as we know now, a fundamental feature of stem cells [1]. A stem cell is a type of cell that is non-specific/specialized in its function; in contrast, for instance, a heart

Generally, we recognize two types of stem cells, embryonic and non-embryonic, with two defining properties. Firstly, they have the capacity of self-renewal, therefore giving rise to more stem cells. Secondly, they are capable of differentiating into

Embryonic stem cells (ESCs) are obtained from 5- to 12-day-old embryos, and they are pluripotent and have a high plasticity as they can differentiate into ectoderm, mesoderm, and endoderm layers, whereas non-embryonic stem cells (non-ESCs) are multipotent, and it appears that they are able to form multiple cell lineages which form an entire tissue, usually specific to one germ layer, e.g., adult

The capability for stem cell potency, in combination with the relative ease to prepare bone marrow stem cell injectates, is an invaluable property for

cells in this exciting new regenerative medicine discipline.

**2**

stem cells [2].

Non-ESCs are undifferentiated, and their proliferation potential compared to embryogenic stem cells is limited, as they have lost their pluripotent capability, placing them lower in the stem cell hierarchy. Nonetheless, it has been suggested that non-ESCs maintain their multipotent differentiation potential. Since they are categorized as allogenic products, they are commercially prepared from several allogenic sources, like amniotic fluid, umbilical cord, and Wharton's jelly [3]. In this chapter we will only deliberate on non-embryotic, autologous adult bone marrow aspirate (BMA)-derived progenitor/stem cells and other bone marrow (BM) stromal cells, prepared at POC with dedicated and approved centrifuges for BM concentration.
