Clinical Use of Stem Cells, Marrow Components, and Other Growth Factors

Chapter 73Clinical Use of Stem Cells, Marrow Components, and Other Growth Factors



Lisa Fortier


Scar tissue that forms after tendon and ligament injuries is architecturally and biomechanically inferior to normal tissues, rendering the structure susceptible to reinjury.1 The goals of regenerative therapies, such as stem cells and growth factors, are to restore normal structure and function to tissues to enhance healing, restore pain-free physical activity, and avoid reinjury. Successful regenerative healing of any tissue is intended to closely mimic events of development in which there are spatial and temporal interactions between scaffold, growth factors, and cell populations. An understanding of the molecular and mechanical processes involved in the development of tendon and ligamentous injuries and between acute and repetitive overload pathologies will help guide development of target therapies for each specific disorder.


For many of the regenerative therapies presently available, technology and marketing are ahead of laboratory and clinical research. Most of the products being used to manage equine tendon and ligament injuries have been evaluated experimentally to some extent, but long-term clinical safety and efficacy data are limited. Ideally, the efficacy data would be obtained using prospective, blinded, and controlled clinical trials, although these studies are exceedingly difficult and expensive to perform. At a minimum, results of new treatments should be compared retrospectively with carefully selected historical case-matched studies. As part of a comprehensive plan, benefits from adjunctive surgical manipulations should also be evaluated. Desmotomy of the accessory ligament (superior [proximal] check ligament) of the superficial digital flexor tendon (SDFT) should be considered for horses with superficial digital flexor (SDF) tendonitis. In areas where a tendon or ligament is anatomically confined by surrounding structures and therefore susceptible to compression, such as the fetlock canal and carpal canal for horses with tendon injuries, as well as the proximal metacarpal/metatarsal regions in horses with enlargement of the proximal aspect of the suspensory ligament, surgical release of the restricting fascia should be implemented as part of a multitargeted approach to tendon/ligament healing. Critical to a successful outcome of all treatment regimens is a carefully implemented rehabilitation program. Well documented in studies of regenerative healing is the importance of mechanical stimulation and the type and quantity of the scaffold, growth factor(s), and/or stem cells.2-6



Stem Cell Therapies


The therapeutic role of stem cells in regenerative medicine is not fully understood. It is unclear whether stem cells ultimately function as a tissue-specific cell, such as a tenocyte, or whether they primarily improve tissue repair through secretion of immunomodulatory and trophic bioactive factors.7 These questions are not purely pedantic in nature because if stem cells are truly immunomodulatory, then allogeneic transplantations should be possible. If allogeneic stem cells were efficacious and could be used safely, then “off-the-shelf” stem cell products could be developed to increase availability and rapid implementation of stem cell therapies.


The stem cell field continues to rapidly evolve experimentally and clinically. At a basic level, stem cells are broadly defined as undifferentiated cells that possess the ability to divide for indefinite periods in culture and may give rise to highly specialized cells of each tissue type (i.e., mesoderm, ectoderm, and endoderm). There are two broad categories of stem cells: embryonic and adult derived (see Hipp and Atala6 and Tweedell8 for recent reviews). Embryonic stem (ES) cells used to be defined as those derived from embryos, more specifically from day 8, preimplantation blastocyts. Using recent advances, ES cells can be generated from adult fibroblasts using many of the same technologies that were used to clone Dolly the sheep. These cells are known as induced pluripotent stem (iPS) cells. Adult-derived mesenchymal stem cells (MSCs) can be obtained from bone marrow, fat, umbilical cord blood, muscle, and many other tissues, including cartilage, trabecular bone, and tendon.6 Hematopoietic stem cells (HSCs) are those cells in bone marrow, which are the basis of bone marrow transplantation, and are capable of forming all types of blood cells. Arguments can be made about the optimal source of stem cells for regenerative therapy; importantly, studies are needed to define the need for stem cells in such endeavors. Presently, stem cell therapies for tendon or ligament regeneration in horses are not regulated by the Food and Drug Administration in the United States or elsewhere.9



Commonly Used Stem Cell Products


Presently, there are three approaches to using stem cell therapy in horses, and all use MSCs, although equine ES, iPS, and umbilical cord blood–derived cells are beginning to be investigated. First, MSCs in a mixed cell population can be harvested from bone marrow aspirates; second, MSCs from bone marrow can be cultured; and third, a mixed cell population of MSCs can be harvested from adipose tissue. Each technique has its strengths and weaknesses.



Bone Marrow–Derived MSCs (BM-MSCs)


BM-MSCs can be easily and noninvasively obtained and compared with other MSCs, and they have a greater capacity to differentiate into other tissue types.10-12 BM-MSCs have received the most scientific attention and hence are the best characterized. The process is straightforward. In standing sedated horses, bone marrow is collected from the sternum or the tuber coxae using local analgesia. Fresh bone marrow is either injected directly into the injured tissue, or the nucleated adherent cell population (containing the BM-MSCs) is isolated and expanded in the laboratory before injection.



Bone Marrow Aspirate and Injection of Fresh Bone Marrow


Bone marrow is aspirated from the sternum at a site where the cranial third of the girth would sit (Figure 73-1

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  2. Thermography: Use in Equine Lameness
  3. Counterirritation
  4. The Carpal Canal and Carpal Synovial Sheath

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Jun 4, 2016 | Posted by in EQUINE MEDICINE | Comments Off on Clinical Use of Stem Cells, Marrow Components, and Other Growth Factors

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