**2. Terminology, history, and background**

The most common types of regenerative medicine therapies include platelet rich plasma (PRP), stem cell therapy from bone marrow aspirate concentrate (BMAC) and adipose tissue grafts, and exosomes. Regenerative therapies are growing worldwide

(**Figure 1**). They are increasing from 164% in 1 year with a total of 4.1 billion dollars in total global funding [2]. These therapies can be used in conjunction or individually, and there is no set algorithm or protocol that dictates superiority [3]. Stem cell therapy in this article will refer to adult stem cells, which are multipotent and have no ethical concerns related to their use, as opposed to embryonic stem cells [4]. Typically, candidates include patients with chronic peripheral joint pain that have not responded to steroid injections, or cannot tolerate the medication due to side effects, including but not limited to hyperglycemia, hypertension, ineffective wound healing, or adrenal gland suppression. Although there is no set protocol, some studies recommend implementing a series of three injections for PRP [5]. However, some physicians may grade progress and response to the initial injection as a rationale for a repeat injection.

#### **2.1 Platelet rich plasma**

PRP is the most common and readily available treatment option. It is the plasma fraction of blood with a high platelet concentration, as well as clotting factors, growth factors, chemokines, cytokines, and other plasma proteins [6]. This therapy helps promote stem cell migration as well as healing [7]. Commonly injected into joints and tendons for repair, PRP was first coined in the 1970's and used to describe the platelet count in peripheral blood, used to transfuse patients with thrombocytopenia [6]. PRP is obtained from blood after centrifuge, which helps separate components based on density gradients (**Figure 2**). Devices used to simplify the preparation of PRP are said to amplify the concentration of PRP 2–5 times the baseline [7]. Despite the limited clinical evidence that exists, PRP has been used to initiate healing for a variety of cases, most commonly including osteoarthritis (OA), lateral epicondylitis, rotator cuff tears, ligament and tendon injuries [7]. Recent randomized control trials actually demonstrate benefit in tendinopathy [7]. It has also been suggested that PRP can play a role in elimination neuropathic pain, thought to be secondary to a cascade of inflammation followed by repair via axon and tissue regeneration [8]. PRP has also been used as an intervertebral disc injection for low

**21**

**2.3 Bone marrow aspirate concentrate**

*Regenerative Medicine*

**2.2 Adipose tissue grafts**

*Blood components after centrifugation.*

**Figure 2.**

*DOI: http://dx.doi.org/10.5772/intechopen.93717*

back pain with promising clinical results, however more randomized controlled trials are needed [3]. Success of this therapy will ultimately depend on the preparation

Stem cell therapy uses non-embryonic adult stem cells described as multipotent stem cells, and in the clinical setting refers to therapy with mesenchymal (often from adipose tissue) and hematopoietic stem cells (often from bone marrow aspirate) [3]. These cells are present in a variety of tissues (adipocytes, chondrocytes, myocytes) and are thought to play a role in immune modulation [3]. The most common source of mesenchymal stem cells (MSC) are found in adipose tissue, first discovered in 1964 by Rodell [2]. There are approximately 500 to 2500× times more MSC's when compared to bone marrow [3]. Adipose derived stem cells (ASC's) are the most promising stem cells identified in humans, since adipose tissue is easily obtained in large quantities with small donor site discomfort [4]. Sites of harvest include the abdomen, upper arm, thigh, and trochanteric fat deposits. Common mechanisms to obtain fat include liposuction or lipectomy, followed by homogenization and enzymatic digestions. Traditional cosmetic liposuction can remove large volume (>4 kg) or small volume (<4 kg) adipose tissue, however for purposes of adipose tissue grafting only 100–200 mL may be needed [9]. The resultant material is then centrifuged. Each gram of adipose tissue yields 5 × 10^3 stem cells, significantly greater than bone marrow [4]. It is important to note that stem cell harvesting is more invasive that a simple blood draw for PRP, and could thus lead to an increase risk for infection or complication for patients undergoing MSC harvesting [10]. If performed under local or tumescent anesthesia, there is minimal to no recovery time. To date, hundreds of trials are listed on the United States National Institutes of Health website (NIH) for the use of ASC's. Examples of applications include soft tissue regeneration, skeletal tissue repair, myocardial infarction, immune disorders such as lupus, multiple sclerosis, Crohn's disease, diabetes.

Bone marrow aspiration is a procedure in which bone marrow is collected, usually from the pelvic iliac crest [11]. The procedure is very similar to PRP, in which the

and composition of the injectate, location, and type and extent of injury.

*Regenerative Medicine DOI: http://dx.doi.org/10.5772/intechopen.93717*

*Pain Management - Practices, Novel Therapies and Bioactives*

(**Figure 1**). They are increasing from 164% in 1 year with a total of 4.1 billion dollars in total global funding [2]. These therapies can be used in conjunction or individually, and there is no set algorithm or protocol that dictates superiority [3]. Stem cell therapy in this article will refer to adult stem cells, which are multipotent and have no ethical concerns related to their use, as opposed to embryonic stem cells [4]. Typically, candidates include patients with chronic peripheral joint pain that have not responded to steroid injections, or cannot tolerate the medication due to side effects, including but not limited to hyperglycemia, hypertension, ineffective wound healing, or adrenal gland suppression. Although there is no set protocol, some studies recommend implementing a series of three injections for PRP [5]. However, some physicians may grade progress and response to the initial injection as a rationale for a repeat injection.

*An atlas of regenerative medicine therapies worldwide. Adapted from alliance for regenerative medicine.*

PRP is the most common and readily available treatment option. It is the plasma

fraction of blood with a high platelet concentration, as well as clotting factors, growth factors, chemokines, cytokines, and other plasma proteins [6]. This therapy helps promote stem cell migration as well as healing [7]. Commonly injected into joints and tendons for repair, PRP was first coined in the 1970's and used to describe the platelet count in peripheral blood, used to transfuse patients with thrombocytopenia [6]. PRP is obtained from blood after centrifuge, which helps separate components based on density gradients (**Figure 2**). Devices used to simplify the preparation of PRP are said to amplify the concentration of PRP 2–5 times the baseline [7]. Despite the limited clinical evidence that exists, PRP has been used to initiate healing for a variety of cases, most commonly including osteoarthritis (OA), lateral epicondylitis, rotator cuff tears, ligament and tendon injuries [7]. Recent randomized control trials actually demonstrate benefit in tendinopathy [7]. It has also been suggested that PRP can play a role in elimination neuropathic pain, thought to be secondary to a cascade of inflammation followed by repair via axon and tissue regeneration [8]. PRP has also been used as an intervertebral disc injection for low

**20**

**2.1 Platelet rich plasma**

**Figure 1.**

**Figure 2.** *Blood components after centrifugation.*

back pain with promising clinical results, however more randomized controlled trials are needed [3]. Success of this therapy will ultimately depend on the preparation and composition of the injectate, location, and type and extent of injury.
