All of these images are of the same patient. Ten days after the injury, early signs of healing are taking place. The bandage was changed at this time. The body is undergoing a healing process that some may consider the fingertip regrowing. About one month after the injury, the wound is now dry.
More soft tissue is now covering the tip of the finger, and a more normal appearance is taking shape. The final image, only seven weeks after the injury occurred, shows a finger that almost looks normal.
Most people would not notice the evidence of the previous injury, and even the nail has resumed a more normal appearance. Dealing with joint pain can cause major disruptions to your day. Sign up and learn how to better take care of your body. Click below and just hit send!
Nelson DL. Welcome to Dr. Nelson's fingertip amputations. Updated October 28, Your Privacy Rights. Nevertheless, long-term studies are necessary to confirm whether these events are associated and if they persist in time after the regeneration process is completed.
Increased vascularization could be transient and a result of increased expression of pro-angiogenic factors in the regenerative microenvironment of the fingertips as we observed in this study. We analyzed the wound fluid that was accumulated under the occlusive dressing over amputated fingertips over the primary phase of regeneration and most probably blastema formation [ 29 ]. We measured high levels of VEGF in the wound fluid that explains increased vascularity which seems to be essential for the complete regeneration in human fingertips.
Interestingly, in mouse models of regeneration, an inverse phenomena is observed where the expression of VEGF is down regulated in blastema [ 11 ] and even induction of angiogenesis by VEGF inhibited the regeneration by altering the transition of blastema to the differentiation phase [ 24 ].
Thus, for the first time, our results reveal discrepancies between mice and human fingertip regeneration. These data along with our observations, suggest an important role for higher blood flow in the fingertip regeneration in mammalians.
In surgical wounds and chronic vascular ulcers, high expression of b-FGF, which is another pro-angiogenic factor, is observed at very early phases of wound healing and the levels further decline over-time during healing [ 31 , 32 ].
We did not detect this growth factor in the accumulative exudates collected at day 7, which is most probably too late for b-FGF expression. A more comprehensive analysis of pro-angiogenic factors over time in fingertip exudate is necessary and will help to determine the factors that control angiogenesis during regeneration.
Deficiency in inflammatory response has been suggested to be an explanation for the absence of fibrotic response during fingertip regeneration [ 33 ]. However, our preliminary data showed that, at least during the first seven days post-amputation in human fingertips, a strong inflammatory response is ongoing in the regenerative microenvironment compared to healing microenvironment of burn wounds as shown in Figure 4.
The central role of inflammation and innate immune response are known in wound healing but still poorly understood in regeneration models [ 34 ], where a prominent expression of inflammatory and immune-related genes was revealed [ 35 , 36 ]. In these models, both pro- and anti-inflammatory cytokines are highly expressed during the first two weeks of regeneration with pro-inflammatory molecules being prominent during the first week and anti-inflammatory cytokines at the second week and after [ 34 ].
Classical models of regeneration such as salamander [ 25 ], Xenopus [ 35 ] or mice digit tip [ 37 ] also show that protein factors triggering the immediate events following traumatic injury are similar in both wound healing and organ regeneration [ 25 , 35 ], but the immune factors that favor one pathway over the other remain unknown.
In our study, pro-inflammatory cytokines were relatively higher expressed in regenerative fingertips than in the burn wound exudates while chemokines where present in lower levels. Further studies should be done to clarify the importance of inflammatory cells and immunity in determining the outcome of the regenerative process. In amphibians and mice, complete regeneration is dependent to nerve-derived growth factors that are secreted by nerve-associated Schwann cell precursors and promote the expansion of blastema and digit regeneration [ 38 , 39 ].
Transcriptome analysis these cells revealed that PDGF, LIF and could be potential paracrine factors that might be important for digit tip regeneration [ 23 ]. The role of enervation as a regeneration triggering factor in humans is not known but our clinical observations with restoration of normal sensitivity seems to reveal an important nerve regeneration process supported by increased expression of growth factors such as BDNF to be active in human fingertips.
Application of occlusive dressing leads to the creation of local permissive niche that provides necessary signals to initiate regeneration which is influenced by local microenvironment rather than systemic factors [ 40 ].
We detected the expression of other growth factors that promote wound reepithelialization, in fingertip exudates such as HGF and EGF that should have a role in the proliferation and further redifferentiation of blastema cell mass.
Further work with higher number of patients is required to establish eventual difference between growth factor profiles and signaling differentiation pathways in regenerating or healing wounds.
Moreover, in this study we were focused only on the first week post-amputation that we considered being crucial for the initiation of regeneration and blastema formation in regenerative fingertips.
In further studies, it would be important to perform sample collection at different time points of regeneration in order to investigate which signaling molecules are involved in different phases of regeneration and how their expression might change over time. Written consent was obtained from all patients, and the procedures were performed in line with the Helsinki Declaration of Recommendations guiding medical doctors in biomedical research involving human subjects.
Fingertip exudates were collected from occlusive dressing at the first dressing change seven days after trauma. Burn wound exudate was collected as described in [ 41 ] and with ethical approval. Briefly, a negative pressure dressing was applied over second-degree burn wounds that collected the accumulated fluid into a reservoir bottle.
Absorbance was read on a Luminex IS device and absorbance data were converted to protein concentrations with Luminex IS Software version 2. Patient samples were tested in triplicate, and the mean value was used for analysis. Control finger was tested first and regenerated fingertip afterwards. Fingertips were tested in 1 and 2 point discrimination. The patient, with closed eyes, stated whether he felt one or two points. We began the test at 15 mm distance and then moved the two points closer until the patient could not discriminate anymore until 4 mm.
The gauge was place between the tip of the thumb and the tip of the concerned finger. The patient applied a spark of maximal power. Pain assessment was performed using visual descriptor scale representing different growing intensities of pain varying from zero to five 0 corresponding to no pain; 1 mild pain; 2 moderate pain; 3 severe pain; 4 very severe pain and 5 worst pain imaginable. Pulp vascularization was measured by power doppler ultrasound test and the elasticity of the regenerative tissue was assessed by the elasticity modulus from Shear Wave Elastography SWE.
Power Doppler sonography is a technique that displays the strength of the Doppler signal in color, rather than the speed and direction information.
It has three times the sensitivity of conventional color Doppler for detection of flow and is particularly useful for small capillaries with low-velocity flow. SWE on the other hand is a technique measures the elasticity of tissue by measuring the propagation speed of shear waves, resulting in mechanical disturbances of ultrasonic waves applied to the tissue by the ultrasound probe [ 42 ].
We first used normal ultrasound imaging in B-mode for topographic orientation and then superimposed and further shear wave elastography mapping in penetration mode. A mapping of the shear wave velocity, from blue soft tissue, low speed to red hard tissue, high speed , produced the first qualitative information. To asses microvascularisation we performed echo-doppler in the same manner.
After positioning of the ultrasound probe in B-mode, and then superimposed the ultrasound Doppler mapping. All images were saved in dicom format. In absence of vascularization, the pixels remained gray or black. Regions that were vascularized appeared in color varying from red to white depending on the intensity. Pixels with Hue between 0 and 60, saturation between 5 and and brightness between 15 and were selected and considered as vascularization.
The percentage of vascularization was calculated as a ratio between vascularization pixels divided by total number of pixels in the evaluation zone. Independent 2-sided t test was used to evaluate statistical difference between the morphological and mechanical characteristics of regenerated fingertips and control healthy fingers. Authors would like to acknowledge Sandra Monnier and Jessie Lamouille for recruiting the patients to the study and their help for sample collection.
National Center for Biotechnology Information , U. Int J Mol Sci. Published online May Allison Cowin, Academic Editor. Author information Article notes Copyright and License information Disclaimer. As I wrote in Nature News : Working with mice, researchers led by Mayumi Ito at New York University have identified a population of stem cells lying beneath the base of the nail that can orchestrate the restoration of a partially amputated digit.
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Environment Planet Possible India bets its energy future on solar—in ways both small and big. Environment As the EU targets emissions cuts, this country has a coal problem. Paid Content How Hong Kong protects its sea sanctuaries. She thawed it out so CNN could take a photograph of the pinky tip alongside her regenerated finger. Here are lessons Kulkarni learned through her pinky ordeal, plus a few from the doctors who worked with her:. I can do my own research.
Srinivasan, the physician who encouraged Kulkarni not to give up, says sometimes doctors don't know about new, cutting-edge treatments being used by other physicians. We weren't going to take no for an answer," she says. Petersen, Kulkarni's surgeon, says he's learned from many patients who've come to him having done research on the internet. Even though you're a stranger, if you write to a doctor who's a leader in the field, you might get an e-mail in return.
Maybe I sounded really desperate. Even if you can't afford to fly out to the expert for treatment, he or she might be able to lead you to a local doctor who can help. Kulkarni said she knows the doctors she saw in the emergency room might have perceived her as an annoying patient when she rejected their treatment options. Be fastidious about keeping records. Sometimes part of my role is to guide them that, in reality, that isn't your problem and I don't recommend that treatment.
Learn more about Elizabeth Cohen's book on being an Empowered Patient. Share this on:.
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